Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of Encenicline, a Selective α7 Nicotinic Receptor Partial Agonist, in Single Ascending-dose and Bioavailability Studies
Encenicline (EVP-6124) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in Alzheimer’s disease and schizophrenia. We report on 2 single-dose studies to assess the relative bioavailability, pharmacokinetic profile, tolerability, and cognitive...
Saved in:
| Published in | Clinical therapeutics Vol. 37; no. 2; pp. 311 - 324 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.02.2015
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 0149-2918 1879-114X 1879-114X |
| DOI | 10.1016/j.clinthera.2014.09.013 |
Cover
| Abstract | Encenicline (EVP-6124) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in Alzheimer’s disease and schizophrenia. We report on 2 single-dose studies to assess the relative bioavailability, pharmacokinetic profile, tolerability, and cognitive effects of encenicline in healthy volunteers.
A single ascending-dose study assessed the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of encenicline in healthy male volunteers. Subjects received a single 1-, 3.5-, 7-, 20-, 60-, or 180-mg oral solution dose of encenicline or placebo. A second single-dose, randomized, open-label, 3-period, crossover study in healthy male and female subjects compared the relative bioavailability of a 1-mg oral capsule versus a 1-mg oral solution dose of encenicline and evaluated the effects of food and sex on encenicline pharmacokinetic profile.
In the first study, encenicline was well tolerated and dose-proportional increases in Cmax (mean range 0.59−100 ng/mL) and AUC0−∞ (mean range 45.6−8890 ng·h/mL) were observed over a 1- to 180-mg dose range. Procognitive effects on the Digit Symbol Substitution Test were maximal at the 20-mg dose. In the second study, encenicline 1-mg oral capsules and oral solution were bioequivalent and there was no observed food effect on encenicline pharmacokinetic profile with the 90% confidence intervals of the treatment ratios for both comparisons (ie, capsule to solution and fed to fasted) for Cmax and AUC being within 80% to 125%. A 30% to 40% higher encenicline exposure in female subjects than respective values in male subjects was consistent with a 33% higher weight of the male subjects. No clinically relevant safety profile or tolerability effects of encenicline were observed.
Encenicline was well tolerated at single doses up to 180 mg, and doses as low as 1 mg had dose- and time-dependent pharmacodynamic effects on the central nervous system. Oral capsule and solution were bioequivalent and were not affected by food. Although a sex effect on pharmacokinetic profile was observed, it was attributable to weight differences. Clinical Trial Registration at EudraCT: 2006-005623-42 and EudracT: 2008-000029-20. |
|---|---|
| AbstractList | Encenicline (EVP-6124) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in Alzheimer's disease and schizophrenia. We report on 2 single-dose studies to assess the relative bioavailability, pharmacokinetic profile, tolerability, and cognitive effects of encenicline in healthy volunteers.PURPOSEEncenicline (EVP-6124) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in Alzheimer's disease and schizophrenia. We report on 2 single-dose studies to assess the relative bioavailability, pharmacokinetic profile, tolerability, and cognitive effects of encenicline in healthy volunteers.A single ascending-dose study assessed the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of encenicline in healthy male volunteers. Subjects received a single 1-, 3.5-, 7-, 20-, 60-, or 180-mg oral solution dose of encenicline or placebo. A second single-dose, randomized, open-label, 3-period, crossover study in healthy male and female subjects compared the relative bioavailability of a 1-mg oral capsule versus a 1-mg oral solution dose of encenicline and evaluated the effects of food and sex on encenicline pharmacokinetic profile.METHODSA single ascending-dose study assessed the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of encenicline in healthy male volunteers. Subjects received a single 1-, 3.5-, 7-, 20-, 60-, or 180-mg oral solution dose of encenicline or placebo. A second single-dose, randomized, open-label, 3-period, crossover study in healthy male and female subjects compared the relative bioavailability of a 1-mg oral capsule versus a 1-mg oral solution dose of encenicline and evaluated the effects of food and sex on encenicline pharmacokinetic profile.In the first study, encenicline was well tolerated and dose-proportional increases in C(max) (mean range 0.59-100 ng/mL) and AUC0-∞ (mean range 45.6-8890 ng·h/mL) were observed over a 1- to 180-mg dose range. Procognitive effects on the Digit Symbol Substitution Test were maximal at the 20-mg dose. In the second study, encenicline 1-mg oral capsules and oral solution were bioequivalent and there was no observed food effect on encenicline pharmacokinetic profile with the 90% confidence intervals of the treatment ratios for both comparisons (ie, capsule to solution and fed to fasted) for Cmax and AUC being within 80% to 125%. A 30% to 40% higher encenicline exposure in female subjects than respective values in male subjects was consistent with a 33% higher weight of the male subjects. No clinically relevant safety profile or tolerability effects of encenicline were observed.FINDINGSIn the first study, encenicline was well tolerated and dose-proportional increases in C(max) (mean range 0.59-100 ng/mL) and AUC0-∞ (mean range 45.6-8890 ng·h/mL) were observed over a 1- to 180-mg dose range. Procognitive effects on the Digit Symbol Substitution Test were maximal at the 20-mg dose. In the second study, encenicline 1-mg oral capsules and oral solution were bioequivalent and there was no observed food effect on encenicline pharmacokinetic profile with the 90% confidence intervals of the treatment ratios for both comparisons (ie, capsule to solution and fed to fasted) for Cmax and AUC being within 80% to 125%. A 30% to 40% higher encenicline exposure in female subjects than respective values in male subjects was consistent with a 33% higher weight of the male subjects. No clinically relevant safety profile or tolerability effects of encenicline were observed.Encenicline was well tolerated at single doses up to 180 mg, and doses as low as 1 mg had dose- and time-dependent pharmacodynamic effects on the central nervous system. Oral capsule and solution were bioequivalent and were not affected by food. Although a sex effect on pharmacokinetic profile was observed, it was attributable to weight differences. Clinical Trial Registration at EudraCT: 2006-005623-42 and EudracT: 2008-000029-20.IMPLICATIONSEncenicline was well tolerated at single doses up to 180 mg, and doses as low as 1 mg had dose- and time-dependent pharmacodynamic effects on the central nervous system. Oral capsule and solution were bioequivalent and were not affected by food. Although a sex effect on pharmacokinetic profile was observed, it was attributable to weight differences. Clinical Trial Registration at EudraCT: 2006-005623-42 and EudracT: 2008-000029-20. Encenicline (EVP-6124) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in Alzheimer’s disease and schizophrenia. We report on 2 single-dose studies to assess the relative bioavailability, pharmacokinetic profile, tolerability, and cognitive effects of encenicline in healthy volunteers. A single ascending-dose study assessed the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of encenicline in healthy male volunteers. Subjects received a single 1-, 3.5-, 7-, 20-, 60-, or 180-mg oral solution dose of encenicline or placebo. A second single-dose, randomized, open-label, 3-period, crossover study in healthy male and female subjects compared the relative bioavailability of a 1-mg oral capsule versus a 1-mg oral solution dose of encenicline and evaluated the effects of food and sex on encenicline pharmacokinetic profile. In the first study, encenicline was well tolerated and dose-proportional increases in Cmax (mean range 0.59−100 ng/mL) and AUC0−∞ (mean range 45.6−8890 ng·h/mL) were observed over a 1- to 180-mg dose range. Procognitive effects on the Digit Symbol Substitution Test were maximal at the 20-mg dose. In the second study, encenicline 1-mg oral capsules and oral solution were bioequivalent and there was no observed food effect on encenicline pharmacokinetic profile with the 90% confidence intervals of the treatment ratios for both comparisons (ie, capsule to solution and fed to fasted) for Cmax and AUC being within 80% to 125%. A 30% to 40% higher encenicline exposure in female subjects than respective values in male subjects was consistent with a 33% higher weight of the male subjects. No clinically relevant safety profile or tolerability effects of encenicline were observed. Encenicline was well tolerated at single doses up to 180 mg, and doses as low as 1 mg had dose- and time-dependent pharmacodynamic effects on the central nervous system. Oral capsule and solution were bioequivalent and were not affected by food. Although a sex effect on pharmacokinetic profile was observed, it was attributable to weight differences. Clinical Trial Registration at EudraCT: 2006-005623-42 and EudracT: 2008-000029-20. Encenicline (EVP-6124) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in Alzheimer's disease and schizophrenia. We report on 2 single-dose studies to assess the relative bioavailability, pharmacokinetic profile, tolerability, and cognitive effects of encenicline in healthy volunteers. A single ascending-dose study assessed the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of encenicline in healthy male volunteers. Subjects received a single 1-, 3.5-, 7-, 20-, 60-, or 180-mg oral solution dose of encenicline or placebo. A second single-dose, randomized, open-label, 3-period, crossover study in healthy male and female subjects compared the relative bioavailability of a 1-mg oral capsule versus a 1-mg oral solution dose of encenicline and evaluated the effects of food and sex on encenicline pharmacokinetic profile. In the first study, encenicline was well tolerated and dose-proportional increases in C(max) (mean range 0.59-100 ng/mL) and AUC0-∞ (mean range 45.6-8890 ng·h/mL) were observed over a 1- to 180-mg dose range. Procognitive effects on the Digit Symbol Substitution Test were maximal at the 20-mg dose. In the second study, encenicline 1-mg oral capsules and oral solution were bioequivalent and there was no observed food effect on encenicline pharmacokinetic profile with the 90% confidence intervals of the treatment ratios for both comparisons (ie, capsule to solution and fed to fasted) for Cmax and AUC being within 80% to 125%. A 30% to 40% higher encenicline exposure in female subjects than respective values in male subjects was consistent with a 33% higher weight of the male subjects. No clinically relevant safety profile or tolerability effects of encenicline were observed. Encenicline was well tolerated at single doses up to 180 mg, and doses as low as 1 mg had dose- and time-dependent pharmacodynamic effects on the central nervous system. Oral capsule and solution were bioequivalent and were not affected by food. Although a sex effect on pharmacokinetic profile was observed, it was attributable to weight differences. Clinical Trial Registration at EudraCT: 2006-005623-42 and EudracT: 2008-000029-20. Abstract Purpose Encenicline (EVP-6124) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in Alzheimer’s disease and schizophrenia. We report on 2 single-dose studies to assess the relative bioavailability, pharmacokinetic profile, tolerability, and cognitive effects of encenicline in healthy volunteers. Methods A single ascending-dose study assessed the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of encenicline in healthy male volunteers. Subjects received a single 1-, 3.5-, 7-, 20-, 60-, or 180-mg oral solution dose of encenicline or placebo. A second single-dose, randomized, open-label, 3-period, crossover study in healthy male and female subjects compared the relative bioavailability of a 1-mg oral capsule versus a 1-mg oral solution dose of encenicline and evaluated the effects of food and sex on encenicline pharmacokinetic profile. Findings In the first study, encenicline was well tolerated and dose-proportional increases in Cmax (mean range 0.59−100 ng/mL) and AUC0−∞ (mean range 45.6−8890 ng·h/mL) were observed over a 1- to 180-mg dose range. Procognitive effects on the Digit Symbol Substitution Test were maximal at the 20-mg dose. In the second study, encenicline 1-mg oral capsules and oral solution were bioequivalent and there was no observed food effect on encenicline pharmacokinetic profile with the 90% confidence intervals of the treatment ratios for both comparisons (ie, capsule to solution and fed to fasted) for Cmax and AUC being within 80% to 125%. A 30% to 40% higher encenicline exposure in female subjects than respective values in male subjects was consistent with a 33% higher weight of the male subjects. No clinically relevant safety profile or tolerability effects of encenicline were observed. Implications Encenicline was well tolerated at single doses up to 180 mg, and doses as low as 1 mg had dose- and time-dependent pharmacodynamic effects on the central nervous system. Oral capsule and solution were bioequivalent and were not affected by food. Although a sex effect on pharmacokinetic profile was observed, it was attributable to weight differences. Clinical Trial Registration at EudraCT: 2006-005623-42 and EudracT: 2008-000029-20. |
| Author | Palfreyman, Michael G. Massaro, Monica Dgetluck, Nancy Barbier, Ann J. Gawryl, Maria Timmerman, Wia Hilt, Dana C. Snyder, Peter Tiessen, Renger Vliet, André Van Hilhorst, Martijn |
| Author_xml | – sequence: 1 givenname: Ann J. surname: Barbier fullname: Barbier, Ann J. organization: Forum Pharmaceuticals, Boston, Massachusetts – sequence: 2 givenname: Martijn surname: Hilhorst fullname: Hilhorst, Martijn organization: PRA International, Zuidlaren, The Netherlands – sequence: 3 givenname: André Van surname: Vliet fullname: Vliet, André Van organization: PRA International, Zuidlaren, The Netherlands – sequence: 4 givenname: Peter surname: Snyder fullname: Snyder, Peter organization: Brown University, Providence, Rhode Island – sequence: 5 givenname: Michael G. surname: Palfreyman fullname: Palfreyman, Michael G. organization: Forum Pharmaceuticals, Boston, Massachusetts – sequence: 6 givenname: Maria surname: Gawryl fullname: Gawryl, Maria organization: Forum Pharmaceuticals, Boston, Massachusetts – sequence: 7 givenname: Nancy surname: Dgetluck fullname: Dgetluck, Nancy organization: Forum Pharmaceuticals, Boston, Massachusetts – sequence: 8 givenname: Monica surname: Massaro fullname: Massaro, Monica organization: Forum Pharmaceuticals, Boston, Massachusetts – sequence: 9 givenname: Renger surname: Tiessen fullname: Tiessen, Renger organization: PRA International, Zuidlaren, The Netherlands – sequence: 10 givenname: Wia surname: Timmerman fullname: Timmerman, Wia organization: PRA International, Zuidlaren, The Netherlands – sequence: 11 givenname: Dana C. surname: Hilt fullname: Hilt, Dana C. email: dhilt@forumpharma.com organization: Forum Pharmaceuticals, Boston, Massachusetts |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25438724$$D View this record in MEDLINE/PubMed |
| BookMark | eNqNUsFuEzEQXaEimhZ-AXzkkA22d9ebPQAKVQtIFVSkSNwsrz3bTrqxg-1Eymdx6G_wTXibhkMlRE-2Zt689zzPR9mBdRay7BWjE0aZeLOY6B5tvAavJpyyckKbCWXFk2zEpnWTM1b-OMhGqdHkvGHTw-wohAWltGgq_iw75FVZTGtejrLbi2vll0o7s7VqiTqMyb5ygxbiXWWuOojbMVHWkEvXJ9EWe4xb4jpyajVYHNxAApA59KAjboD8_lWTL6hdxNQm30DDKjpPLpSPqHoyu3IWQxwTtGSO9qoHMguJyqR7blyAO7UP6NRGYb8XnMe1QQjPs6ed6gO8uD-Ps-9np5cnn_Lzrx8_n8zOc11NeZELU2jRJvPC1F1XgzKV7jhVvEwVxttOCFYXpuXMVKJtGdBGgalawTpeiK4tjrPXO96Vdz_XEKJcYjLZ98qCWwfJhKAl43VRJejLe-i6XYKRK49L5bdyv-oEeLsDaO9C8NBJjVFFdDb69ELJqByilQv5N1o5RCtpI1O0ab5-ML-X-P_kbDcJaVUbBC-DRki5GfQpLGkcPoLj3QOOAYda9TewhbBwa29TEpLJwCWV8-HrDT-PlZQKWg37ef9vgkdZ-AM74vLC |
| CitedBy_id | crossref_primary_10_1016_j_clinthera_2015_01_004 crossref_primary_10_1124_pr_113_008581 crossref_primary_10_1016_j_bcp_2015_07_006 crossref_primary_10_1016_j_clinthera_2015_01_005 crossref_primary_10_1038_npp_2015_176 crossref_primary_10_1093_ntr_nty116 crossref_primary_10_1021_acs_jmedchem_6b01506 crossref_primary_10_4103_1673_5374_165309 crossref_primary_10_1371_journal_pone_0187609 crossref_primary_10_1016_j_ejmech_2018_12_023 crossref_primary_10_1021_acsmedchemlett_7b00032 crossref_primary_10_2174_1574887116666210204125844 crossref_primary_10_1016_j_psc_2016_01_005 crossref_primary_10_3389_fnimg_2024_1358221 crossref_primary_10_1254_fpj_153_28 crossref_primary_10_1517_14656566_2016_1149164 crossref_primary_10_17116_jnevro20161168177_87 crossref_primary_10_1016_j_neuropharm_2016_07_010 crossref_primary_10_3390_toxins7051683 crossref_primary_10_1124_pharmrev_120_000097 crossref_primary_10_1016_j_ejpb_2019_12_014 crossref_primary_10_1016_j_ejphar_2017_05_058 crossref_primary_10_1007_s11095_024_03690_6 crossref_primary_10_3390_md21060368 crossref_primary_10_1080_13543784_2020_1764938 crossref_primary_10_1038_srep25659 crossref_primary_10_1097_JCP_0000000000000919 crossref_primary_10_1016_j_trci_2019_02_002 crossref_primary_10_1080_1061186X_2018_1474361 crossref_primary_10_1016_j_apsb_2017_09_001 crossref_primary_10_3390_cells9122655 crossref_primary_10_4155_fmc_15_143 crossref_primary_10_1007_s00404_017_4363_3 crossref_primary_10_1016_j_bmcl_2017_10_009 crossref_primary_10_1016_j_coph_2017_12_003 crossref_primary_10_1080_13543776_2018_1455827 crossref_primary_10_1517_13543784_2016_1121995 crossref_primary_10_1016_j_npep_2018_12_003 |
| Cites_doi | 10.1111/j.1527-3458.2004.tb00010.x 10.1001/archpsyc.63.6.630 10.1016/0013-4694(86)90184-7 10.1038/sj.npp.1300028 10.2174/138161206775474224 10.1038/npp.2009.196 10.1016/S0022-3565(24)35076-1 10.1007/s00213-003-1482-2 10.1007/s007020170006 10.2174/092986706777442011 10.1038/34413 10.1124/jpet.104.076968 10.1124/mi.4.5.8 10.1016/j.neuropharm.2011.10.024 10.2174/1871524911006030180 10.1016/0014-2999(96)00010-6 10.1016/j.neulet.2006.09.061 10.1097/JGP.0b013e3181e446c8 10.1111/j.1460-9568.2005.04560.x 10.1002/cpt1971122part1245 10.1185/030079903125001631 10.1016/j.euroneuro.2005.03.006 10.1001/archneur.1994.00540150074020 10.1002/med.10037 10.1007/978-3-540-69248-5_7 10.1007/BF02246281 10.1007/s002130050931 10.1007/s00213-006-0675-x 10.1016/S0006-3223(00)01094-5 10.1002/neu.10109 10.2174/138161210790170094 10.1016/j.biopsych.2010.08.006 10.1038/sj.npp.1300450 10.1517/13543776.15.9.1221 10.1038/sj.npp.1301188 10.1111/j.2044-8341.1974.tb02285.x 10.1016/j.pharmthera.2009.03.009 10.1027/1618-3169.52.2.99 10.1176/jnp.11.2.190 |
| ContentType | Journal Article |
| Copyright | 2015 The Authors The Authors Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. |
| Copyright_xml | – notice: 2015 The Authors – notice: The Authors – notice: Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. |
| DBID | 6I. AAFTH AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1016/j.clinthera.2014.09.013 |
| DatabaseName | ScienceDirect Open Access Titles Elsevier:ScienceDirect:Open Access CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine Pharmacy, Therapeutics, & Pharmacology |
| EISSN | 1879-114X |
| EndPage | 324 |
| ExternalDocumentID | 25438724 10_1016_j_clinthera_2014_09_013 S0149291814006055 1_s2_0_S0149291814006055 |
| Genre | Randomized Controlled Trial Research Support, Non-U.S. Gov't Journal Article |
| GroupedDBID | --- --K --M .1- .FO .~1 0R~ 123 1P~ 1~. 1~5 29B 4.4 457 4G. 5RE 5VS 6J9 6PF 7-5 71M 7RV 7X7 88E 8AO 8FI 8FJ 8G5 8P~ AABNK AAEDT AAEDW AAIKJ AAKOC AALRI AAOAW AAQFI AATTM AAWTL AAXKI AAXUO ABBQC ABFNM ABFRF ABJNI ABMAC ABMZM ABUWG ABZDS ACDAQ ACIEU ACPRK ACRLP ACVFH ADBBV ADCNI ADEZE ADFRT AEBSH AEFWE AEIPS AEKER AENEX AEUPX AEVXI AFKRA AFPUW AFRAH AFRHN AFTJW AFXIZ AGCQF AGUBO AGYEJ AHMBA AIEXJ AIIUN AIKHN AITUG AJRQY AJUYK AKBMS AKRWK AKYEP ALCLG ALMA_UNASSIGNED_HOLDINGS AMRAJ ANKPU ANZVX AQUVI AXJTR AZQEC BENPR BKEYQ BKOJK BLXMC BNPGV BPHCQ BVXVI CCPQU CS3 DU5 DWQXO EBS EFJIC EFKBS EJD EMOBN EO8 EO9 EP2 EP3 EX3 F5P FDB FEDTE FIRID FNPLU FYGXN FYUFA G-Q GBLVA GNUQQ GUQSH HMCUK HVGLF J1W KOM M0T M1P M2O M41 MO0 N9A NAPCQ O-L O9- OAUVE OD~ OGGZJ OO0 OZT P-8 P-9 PC. PHGZM PHGZT PJZUB PPXIY PQQKQ PROAC PSQYO PUEGO Q38 ROL RPZ SCC SDF SDG SEL SES SPCBC SSH SSP SSZ SV3 T5K UKHRP WH7 WOW Z5R ~G- .GJ 0SF 1B1 3V. 53G AACTN AAQQT AAQXK AAYOK ABWVN ABXDB ACRPL ADMUD ADNMO ADVLN AFCTW AFFNX AFJKZ AFKWA AGHFR AJOXV ALIPV AMFUW ASPBG AVWKF AZFZN FGOYB HZ~ H~9 IHE NCXOZ R2- RIG SEW UHS XOL ZGI ZXP 6I. AAFTH AAIAV AATCM ABLVK ABYKQ AJBFU EFLBG LCYCR AAYWO AAYXX ACLOT AGQPQ AIGII APXCP CITATION ~HD AGRNS CGR CUY CVF ECM EIF NPM 7X8 |
| ID | FETCH-LOGICAL-c5823-6d3c6bafe6d7ff7ead5cf20a24e6d12bf66173db21d56bb1e09aed5b61f236fb3 |
| IEDL.DBID | .~1 |
| ISSN | 0149-2918 1879-114X |
| IngestDate | Sun Sep 28 11:23:27 EDT 2025 Mon Jul 21 06:08:55 EDT 2025 Wed Oct 01 06:31:02 EDT 2025 Thu Apr 24 23:11:30 EDT 2025 Fri Feb 23 02:30:12 EST 2024 Sun Feb 23 10:18:51 EST 2025 Tue Aug 26 16:34:09 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 2 |
| Keywords | encenicline cognition α7 nicotinic acetylcholine receptor agonist pharmacokinetic profile bioavailability pharmacodynamics α 7 nicotinic acetylcholine receptor agonist α nicotinic acetylcholine receptor agonist |
| Language | English |
| License | http://creativecommons.org/licenses/by-nc-nd/3.0 https://www.elsevier.com/tdm/userlicense/1.0 Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c5823-6d3c6bafe6d7ff7ead5cf20a24e6d12bf66173db21d56bb1e09aed5b61f236fb3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 |
| OpenAccessLink | https://www.sciencedirect.com/science/article/pii/S0149291814006055 |
| PMID | 25438724 |
| PQID | 1660412735 |
| PQPubID | 23479 |
| PageCount | 14 |
| ParticipantIDs | proquest_miscellaneous_1660412735 pubmed_primary_25438724 crossref_citationtrail_10_1016_j_clinthera_2014_09_013 crossref_primary_10_1016_j_clinthera_2014_09_013 elsevier_sciencedirect_doi_10_1016_j_clinthera_2014_09_013 elsevier_clinicalkeyesjournals_1_s2_0_S0149291814006055 elsevier_clinicalkey_doi_10_1016_j_clinthera_2014_09_013 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2015-02-01 |
| PublicationDateYYYYMMDD | 2015-02-01 |
| PublicationDate_xml | – month: 02 year: 2015 text: 2015-02-01 day: 01 |
| PublicationDecade | 2010 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Clinical therapeutics |
| PublicationTitleAlternate | Clin Ther |
| PublicationYear | 2015 |
| Publisher | Elsevier Inc |
| Publisher_xml | – name: Elsevier Inc |
| References | Romanelli, Gualtieri (bib14) 2003; 23 White, Levin (bib4) 1999; 143 Mazurov, Hauser, Miller (bib16) 2006; 13 Tregellas, Olincy, Johnson (bib26) 2010; 35 Olincy, Harris, Johnson (bib25) 2006; 63 Kitagawa, Takenouchi, Azuma (bib24) 2003; 8 Buccafusco (bib8) 2004; 4 Robinson, Merskey, Blume (bib40) 1994; 51 Bourin, Ripoll, Dailly (bib15) 2003; 19 Dunbar, Boeijinga, Demazières (bib39) 2007; 191 Martin, Sloan, Sapira, Jasinski (bib28) 1971; 12 Bond, Lader (bib29) 1974; 47 Thomsen, Hansen, Timmerman, Mikkelsen (bib10) 2010; 16 Toledano, Alvarez, Toledano-Díaz (bib6) 2010; 10 Gündisch (bib13) 2005; 15 Kogan, Korczyn, Virchovsky (bib34) 2001; 108 Rezvani, Levin (bib1) 2001; 49 Curzon, Anderson, Nikkel (bib9) 2006; 410 Leiser, Bowlby, Comery, Dunlop (bib11) 2009; 122 Adler, Brassen (bib35) 2001; 43 D’Andrea, Nagele (bib12) 2006; 12 Gatto, Bohme, Caldwell (bib7) 2004; 10 Bergis, Pichat, Santamaria (bib17) 2004; 583 Picciotto, Zoli, Rimondini (bib18) 1998; 391 Brioni, Kim, O’Neill (bib20) 1996; 303 Quick, Lester (bib5) 2002; 53 Klimesch, Schack, Sauseng (bib32) 2005; 52 Pichat, Bergis, Terranova (bib22) 2007; 32 Barik, Wonnacott (bib19) 2009; 192 Prickaerts Jos, van Goethem, Chesworth (bib27) 2012; 62 Harris, Kongs, Allensworth (bib2) 2004; 29 O’Neill, Rieger, Kem, Stevens (bib23) 2003; 169 Hajós, Hurst, Hoffman (bib38) 2005; 312 Kinney, Patino, Mermet-Bouvier (bib33) 1999; 291 Siok, Rogers, Kocsis, Hajós (bib37) 2006; 23 Levin, Conners, Sparrow (bib3) 1996; 123 Emanuel, Lopez, Houck (bib31) 2011; 19 Dimpfel (bib36) 2005; 15 Hughes, John (bib42) 1999; 11 Wechsler (bib30) 1939 Castner, Smagin, Piser (bib21) 2011; 69 Brenner, Ulrich, Spiker (bib41) 1986; 64 Emanuel (10.1016/j.clinthera.2014.09.013_bib31) 2011; 19 Kogan (10.1016/j.clinthera.2014.09.013_bib34) 2001; 108 Gatto (10.1016/j.clinthera.2014.09.013_bib7) 2004; 10 Pichat (10.1016/j.clinthera.2014.09.013_bib22) 2007; 32 Toledano (10.1016/j.clinthera.2014.09.013_bib6) 2010; 10 Adler (10.1016/j.clinthera.2014.09.013_bib35) 2001; 43 Dunbar (10.1016/j.clinthera.2014.09.013_bib39) 2007; 191 Castner (10.1016/j.clinthera.2014.09.013_bib21) 2011; 69 Tregellas (10.1016/j.clinthera.2014.09.013_bib26) 2010; 35 Klimesch (10.1016/j.clinthera.2014.09.013_bib32) 2005; 52 Bond (10.1016/j.clinthera.2014.09.013_bib29) 1974; 47 Hajós (10.1016/j.clinthera.2014.09.013_bib38) 2005; 312 Siok (10.1016/j.clinthera.2014.09.013_bib37) 2006; 23 Martin (10.1016/j.clinthera.2014.09.013_bib28) 1971; 12 Leiser (10.1016/j.clinthera.2014.09.013_bib11) 2009; 122 Buccafusco (10.1016/j.clinthera.2014.09.013_bib8) 2004; 4 Prickaerts Jos (10.1016/j.clinthera.2014.09.013_bib27) 2012; 62 Gündisch (10.1016/j.clinthera.2014.09.013_bib13) 2005; 15 Bergis (10.1016/j.clinthera.2014.09.013_bib17) 2004; 583 Curzon (10.1016/j.clinthera.2014.09.013_bib9) 2006; 410 Wechsler (10.1016/j.clinthera.2014.09.013_bib30) 1939 Olincy (10.1016/j.clinthera.2014.09.013_bib25) 2006; 63 Romanelli (10.1016/j.clinthera.2014.09.013_bib14) 2003; 23 Thomsen (10.1016/j.clinthera.2014.09.013_bib10) 2010; 16 Robinson (10.1016/j.clinthera.2014.09.013_bib40) 1994; 51 Picciotto (10.1016/j.clinthera.2014.09.013_bib18) 1998; 391 Barik (10.1016/j.clinthera.2014.09.013_bib19) 2009; 192 Brenner (10.1016/j.clinthera.2014.09.013_bib41) 1986; 64 Quick (10.1016/j.clinthera.2014.09.013_bib5) 2002; 53 Bourin (10.1016/j.clinthera.2014.09.013_bib15) 2003; 19 O’Neill (10.1016/j.clinthera.2014.09.013_bib23) 2003; 169 Harris (10.1016/j.clinthera.2014.09.013_bib2) 2004; 29 White (10.1016/j.clinthera.2014.09.013_bib4) 1999; 143 Mazurov (10.1016/j.clinthera.2014.09.013_bib16) 2006; 13 Levin (10.1016/j.clinthera.2014.09.013_bib3) 1996; 123 Kinney (10.1016/j.clinthera.2014.09.013_bib33) 1999; 291 Hughes (10.1016/j.clinthera.2014.09.013_bib42) 1999; 11 Rezvani (10.1016/j.clinthera.2014.09.013_bib1) 2001; 49 D’Andrea (10.1016/j.clinthera.2014.09.013_bib12) 2006; 12 Kitagawa (10.1016/j.clinthera.2014.09.013_bib24) 2003; 8 Brioni (10.1016/j.clinthera.2014.09.013_bib20) 1996; 303 Dimpfel (10.1016/j.clinthera.2014.09.013_bib36) 2005; 15 |
| References_xml | – volume: 11 start-page: 190 year: 1999 end-page: 208 ident: bib42 article-title: Conventional and quantitative electroencephalography in psychiatry publication-title: J Neuropsychiatry Clin Neurosci – volume: 52 start-page: 99 year: 2005 end-page: 108 ident: bib32 article-title: The functional significance of Theta and Upper Alpha oscillations publication-title: Exp Psychol – volume: 108 start-page: 1167 year: 2001 end-page: 1173 ident: bib34 article-title: EEG changes during long-term treatment with donepezil in Alzheimer’s disease patients publication-title: J Neural Transm – volume: 15 start-page: 673 year: 2005 end-page: 682 ident: bib36 article-title: Pharmacological modulation of cholinergic brain activity and its reflection in special EEG frequency changes from various brain areas in the freely moving rat (Tele-stereo-EEG) publication-title: Eur Neuropsychopharmacol – volume: 291 start-page: 99 year: 1999 end-page: 106 ident: bib33 article-title: Cognition-enhancing drugs increase stimulated hippocampal θ rhythm amplitude in the urethane-anesthetized rat publication-title: J Pharmacol Exp Ther – volume: 123 start-page: 55 year: 1996 end-page: 63 ident: bib3 article-title: Nicotine effects on adults with attention-deficit/hyperactivity disorder publication-title: Psychopharmacology – volume: 12 start-page: 245 year: 1971 end-page: 258 ident: bib28 article-title: Physiologic, subjective and behavioural effects of amphetamine, metamphetamine, phenmetrazine and methylphenidate publication-title: Clin Pharmacol Ther – volume: 23 start-page: 393 year: 2003 end-page: 426 ident: bib14 article-title: Cholinergic nicotinic receptors: competitive ligands, allosteric modulators and their potential applications publication-title: Med Res Rev – volume: 4 start-page: 285 year: 2004 end-page: 295 ident: bib8 article-title: Neuronal nicotinic receptor subtypes: defining therapeutic targets publication-title: Mol Interv – volume: 13 start-page: 1567 year: 2006 end-page: 1584 ident: bib16 article-title: Selective α publication-title: Curr Med Chem – volume: 191 start-page: 919 year: 2007 end-page: 929 ident: bib39 article-title: Effects of TC-1734 (AZD3480), a selective neuronal nicotinic agonist, on cognitive performance and the EEG of young healthy male volunteers publication-title: Psychopharmacology – volume: 16 start-page: 323 year: 2010 end-page: 343 ident: bib10 article-title: Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology publication-title: Curr Pharm Des – volume: 64 start-page: 483 year: 1986 end-page: 492 ident: bib41 article-title: Computerized EEG spectral analysis in elderly normal, demented and depressed subjects publication-title: Electroencephalogr Clin Neurophys – volume: 63 start-page: 630 year: 2006 end-page: 638 ident: bib25 article-title: Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia publication-title: Arch Gen Psychiatry – volume: 23 start-page: 571 year: 2006 end-page: 574 ident: bib37 article-title: Activation of alpha7 acetylcholine receptors augments stimulation-induced hippocampal theta oscillation publication-title: Eur J Neurosci – volume: 10 start-page: 180 year: 2010 end-page: 206 ident: bib6 article-title: Diversity and variability of the effects of nicotine on different cortical regions of the brain—therapeutic and toxicological implications publication-title: Cent Nerv Syst Agents Med Chem – volume: 49 start-page: 258 year: 2001 end-page: 267 ident: bib1 article-title: Cognitive effects of nicotine publication-title: Biol Psychiatry – volume: 19 start-page: 160 year: 2011 end-page: 168 ident: bib31 article-title: Trajectory of cognitive decline as a predictor of psychosis in early Alzheimer disease in the cardiovascular health study publication-title: Am J Geriatr Psychiatry – volume: 122 start-page: 302 year: 2009 end-page: 311 ident: bib11 article-title: A cog in cognition: how the alpha 7 nicotinic acetylcholine receptor is geared towards improving cognitive deficits publication-title: Pharmacol Ther – volume: 8 start-page: 542 year: 2003 end-page: 551 ident: bib24 article-title: Safety, pharmacokinetics and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers publication-title: Neuropsychopharmacology – volume: 391 start-page: 173 year: 1998 end-page: 177 ident: bib18 article-title: Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine publication-title: Nature – volume: 62 start-page: 1099 year: 2012 end-page: 1110 ident: bib27 article-title: EVP-6124, a novel and selective α7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors publication-title: Neuropharmacology – volume: 32 start-page: 17 year: 2007 end-page: 34 ident: bib22 article-title: SSR180711, a novel selective α7 nicotinic receptor partial agonist: (II) Efficacy in experimental models predictive of activity against cognitive symptoms of schizophrenia publication-title: Neuropsychopharmacology – volume: 303 start-page: 1 year: 1996 end-page: 5 ident: bib20 article-title: Nicotine cue: lack of effect of the alpha 7 nicotinic receptor antagonist methyllycaconitine publication-title: Eur J Pharmacol – start-page: 229 year: 1939 ident: bib30 publication-title: The Measurement of Adult Intelligence – volume: 53 start-page: 457 year: 2002 end-page: 478 ident: bib5 article-title: Desensitization of neuronal nicotinic receptors publication-title: J Neurobiol – volume: 35 start-page: 938 year: 2010 end-page: 942 ident: bib26 article-title: Functional magnetic resonance imaging of effects of a nicotinic agonist in schizophrenia publication-title: Neuropsychopharmacology – volume: 312 start-page: 1213 year: 2005 end-page: 1222 ident: bib38 article-title: The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-azabicyclo[2.2.2.]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats publication-title: J Pharmacol Exp Ther – volume: 143 start-page: 158 year: 1999 end-page: 165 ident: bib4 article-title: Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s Disease publication-title: Psychopharmacology – volume: 51 start-page: 280 year: 1994 end-page: 284 ident: bib40 article-title: Electroencephalography as an aid in the exclusion of Alzheimer׳s disease publication-title: Arch Neurol – volume: 19 start-page: 169 year: 2003 end-page: 177 ident: bib15 article-title: Nicotinic receptors and Alzheimer’s disease publication-title: Curr Med Res Opin – volume: 10 start-page: 147 year: 2004 end-page: 166 ident: bib7 article-title: TC-1734: an orally active neuronal nicotinic acetylcholine receptor modulator with antidepressant, neuroprotective and long-lasting cognitive effects publication-title: CNS Drug Rev – volume: 29 start-page: 1378 year: 2004 end-page: 1385 ident: bib2 article-title: Effect of nicotine on cognitive deficits in schizophrenia publication-title: Neuropsychopharmacology – volume: 69 start-page: 12 year: 2011 end-page: 18 ident: bib21 article-title: Immediate and sustained improvements in working memory after selective stimulation of α7 nicotinic acetylcholine receptors – volume: 43 start-page: 273 year: 2001 end-page: 276 ident: bib35 article-title: Short-term Rivastigmine treatment reduces EEG slow-wave power in Alzheimer patients publication-title: Pharmacoelectroencephalography – volume: 15 start-page: 1221 year: 2005 end-page: 1239 ident: bib13 article-title: Nicotinic acetylcholine receptor ligands as potential therapeutics publication-title: Exp Opin Ther Patents – volume: 169 start-page: 332 year: 2003 end-page: 339 ident: bib23 article-title: DMXB, An α publication-title: Psychopharmacology – volume: 192 start-page: 173 year: 2009 end-page: 207 ident: bib19 article-title: Molecular and cellular mechanisms of action of nicotine in the CNS publication-title: Handb Exp Pharmacol – volume: 583 start-page: 2 year: 2004 ident: bib17 article-title: SSR180711A, a novel selective α7 nicotine receptor partial agonist II effects in models predictive of therapeutic activity on cognitive symptoms of Alzheimer’s Disease publication-title: Soc Neurosci – volume: 47 start-page: 211 year: 1974 end-page: 218 ident: bib29 article-title: The use of analogue scales in rating subjective feelings publication-title: Br J Med Psychol – volume: 12 start-page: 677 year: 2006 end-page: 684 ident: bib12 article-title: Targeting the alpha 7 nicotinic acetylcholine receptor to reduce amyloid accumulation in Alzheimer׳s disease pyramidal neurons publication-title: Curr Pharm Des – volume: 410 start-page: 15 year: 2006 end-page: 19 ident: bib9 article-title: Antisense knockdown of the rat α7 nicotinic acetylcholine receptor produces spatial memory impairment publication-title: Neurosci Lett – volume: 10 start-page: 147 year: 2004 ident: 10.1016/j.clinthera.2014.09.013_bib7 article-title: TC-1734: an orally active neuronal nicotinic acetylcholine receptor modulator with antidepressant, neuroprotective and long-lasting cognitive effects publication-title: CNS Drug Rev doi: 10.1111/j.1527-3458.2004.tb00010.x – volume: 63 start-page: 630 year: 2006 ident: 10.1016/j.clinthera.2014.09.013_bib25 article-title: Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia publication-title: Arch Gen Psychiatry doi: 10.1001/archpsyc.63.6.630 – volume: 64 start-page: 483 year: 1986 ident: 10.1016/j.clinthera.2014.09.013_bib41 article-title: Computerized EEG spectral analysis in elderly normal, demented and depressed subjects publication-title: Electroencephalogr Clin Neurophys doi: 10.1016/0013-4694(86)90184-7 – volume: 8 start-page: 542 year: 2003 ident: 10.1016/j.clinthera.2014.09.013_bib24 article-title: Safety, pharmacokinetics and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers publication-title: Neuropsychopharmacology doi: 10.1038/sj.npp.1300028 – volume: 12 start-page: 677 year: 2006 ident: 10.1016/j.clinthera.2014.09.013_bib12 article-title: Targeting the alpha 7 nicotinic acetylcholine receptor to reduce amyloid accumulation in Alzheimer׳s disease pyramidal neurons publication-title: Curr Pharm Des doi: 10.2174/138161206775474224 – volume: 35 start-page: 938 year: 2010 ident: 10.1016/j.clinthera.2014.09.013_bib26 article-title: Functional magnetic resonance imaging of effects of a nicotinic agonist in schizophrenia publication-title: Neuropsychopharmacology doi: 10.1038/npp.2009.196 – volume: 291 start-page: 99 year: 1999 ident: 10.1016/j.clinthera.2014.09.013_bib33 article-title: Cognition-enhancing drugs increase stimulated hippocampal θ rhythm amplitude in the urethane-anesthetized rat publication-title: J Pharmacol Exp Ther doi: 10.1016/S0022-3565(24)35076-1 – volume: 169 start-page: 332 year: 2003 ident: 10.1016/j.clinthera.2014.09.013_bib23 article-title: DMXB, An α7 nicotinic agonist, normalizes auditory gating in isolation-reared rats publication-title: Psychopharmacology doi: 10.1007/s00213-003-1482-2 – volume: 108 start-page: 1167 year: 2001 ident: 10.1016/j.clinthera.2014.09.013_bib34 article-title: EEG changes during long-term treatment with donepezil in Alzheimer’s disease patients publication-title: J Neural Transm doi: 10.1007/s007020170006 – volume: 13 start-page: 1567 year: 2006 ident: 10.1016/j.clinthera.2014.09.013_bib16 article-title: Selective α7 nicotinic acetylcholine receptor agonists publication-title: Curr Med Chem doi: 10.2174/092986706777442011 – volume: 391 start-page: 173 year: 1998 ident: 10.1016/j.clinthera.2014.09.013_bib18 article-title: Acetylcholine receptors containing the beta2 subunit are involved in the reinforcing properties of nicotine publication-title: Nature doi: 10.1038/34413 – volume: 312 start-page: 1213 year: 2005 ident: 10.1016/j.clinthera.2014.09.013_bib38 article-title: The selective alpha7 nicotinic acetylcholine receptor agonist PNU-282987 [N-[(3R)-1-azabicyclo[2.2.2.]oct-3-yl]-4-chlorobenzamide hydrochloride] enhances GABAergic synaptic activity in brain slices and restores auditory gating deficits in anesthetized rats publication-title: J Pharmacol Exp Ther doi: 10.1124/jpet.104.076968 – volume: 4 start-page: 285 year: 2004 ident: 10.1016/j.clinthera.2014.09.013_bib8 article-title: Neuronal nicotinic receptor subtypes: defining therapeutic targets publication-title: Mol Interv doi: 10.1124/mi.4.5.8 – volume: 62 start-page: 1099 year: 2012 ident: 10.1016/j.clinthera.2014.09.013_bib27 article-title: EVP-6124, a novel and selective α7 nicotinic acetylcholine receptor partial agonist, improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors publication-title: Neuropharmacology doi: 10.1016/j.neuropharm.2011.10.024 – volume: 10 start-page: 180 year: 2010 ident: 10.1016/j.clinthera.2014.09.013_bib6 article-title: Diversity and variability of the effects of nicotine on different cortical regions of the brain—therapeutic and toxicological implications publication-title: Cent Nerv Syst Agents Med Chem doi: 10.2174/1871524911006030180 – volume: 303 start-page: 1 year: 1996 ident: 10.1016/j.clinthera.2014.09.013_bib20 article-title: Nicotine cue: lack of effect of the alpha 7 nicotinic receptor antagonist methyllycaconitine publication-title: Eur J Pharmacol doi: 10.1016/0014-2999(96)00010-6 – volume: 410 start-page: 15 year: 2006 ident: 10.1016/j.clinthera.2014.09.013_bib9 article-title: Antisense knockdown of the rat α7 nicotinic acetylcholine receptor produces spatial memory impairment publication-title: Neurosci Lett doi: 10.1016/j.neulet.2006.09.061 – volume: 19 start-page: 160 year: 2011 ident: 10.1016/j.clinthera.2014.09.013_bib31 article-title: Trajectory of cognitive decline as a predictor of psychosis in early Alzheimer disease in the cardiovascular health study publication-title: Am J Geriatr Psychiatry doi: 10.1097/JGP.0b013e3181e446c8 – volume: 23 start-page: 571 year: 2006 ident: 10.1016/j.clinthera.2014.09.013_bib37 article-title: Activation of alpha7 acetylcholine receptors augments stimulation-induced hippocampal theta oscillation publication-title: Eur J Neurosci doi: 10.1111/j.1460-9568.2005.04560.x – volume: 12 start-page: 245 year: 1971 ident: 10.1016/j.clinthera.2014.09.013_bib28 article-title: Physiologic, subjective and behavioural effects of amphetamine, metamphetamine, phenmetrazine and methylphenidate publication-title: Clin Pharmacol Ther doi: 10.1002/cpt1971122part1245 – volume: 19 start-page: 169 year: 2003 ident: 10.1016/j.clinthera.2014.09.013_bib15 article-title: Nicotinic receptors and Alzheimer’s disease publication-title: Curr Med Res Opin doi: 10.1185/030079903125001631 – volume: 15 start-page: 673 year: 2005 ident: 10.1016/j.clinthera.2014.09.013_bib36 article-title: Pharmacological modulation of cholinergic brain activity and its reflection in special EEG frequency changes from various brain areas in the freely moving rat (Tele-stereo-EEG) publication-title: Eur Neuropsychopharmacol doi: 10.1016/j.euroneuro.2005.03.006 – volume: 51 start-page: 280 year: 1994 ident: 10.1016/j.clinthera.2014.09.013_bib40 article-title: Electroencephalography as an aid in the exclusion of Alzheimer׳s disease publication-title: Arch Neurol doi: 10.1001/archneur.1994.00540150074020 – volume: 23 start-page: 393 year: 2003 ident: 10.1016/j.clinthera.2014.09.013_bib14 article-title: Cholinergic nicotinic receptors: competitive ligands, allosteric modulators and their potential applications publication-title: Med Res Rev doi: 10.1002/med.10037 – volume: 192 start-page: 173 year: 2009 ident: 10.1016/j.clinthera.2014.09.013_bib19 article-title: Molecular and cellular mechanisms of action of nicotine in the CNS publication-title: Handb Exp Pharmacol doi: 10.1007/978-3-540-69248-5_7 – volume: 123 start-page: 55 year: 1996 ident: 10.1016/j.clinthera.2014.09.013_bib3 article-title: Nicotine effects on adults with attention-deficit/hyperactivity disorder publication-title: Psychopharmacology doi: 10.1007/BF02246281 – volume: 143 start-page: 158 year: 1999 ident: 10.1016/j.clinthera.2014.09.013_bib4 article-title: Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s Disease publication-title: Psychopharmacology doi: 10.1007/s002130050931 – volume: 191 start-page: 919 year: 2007 ident: 10.1016/j.clinthera.2014.09.013_bib39 article-title: Effects of TC-1734 (AZD3480), a selective neuronal nicotinic agonist, on cognitive performance and the EEG of young healthy male volunteers publication-title: Psychopharmacology doi: 10.1007/s00213-006-0675-x – volume: 49 start-page: 258 year: 2001 ident: 10.1016/j.clinthera.2014.09.013_bib1 article-title: Cognitive effects of nicotine publication-title: Biol Psychiatry doi: 10.1016/S0006-3223(00)01094-5 – start-page: 229 year: 1939 ident: 10.1016/j.clinthera.2014.09.013_bib30 – volume: 53 start-page: 457 year: 2002 ident: 10.1016/j.clinthera.2014.09.013_bib5 article-title: Desensitization of neuronal nicotinic receptors publication-title: J Neurobiol doi: 10.1002/neu.10109 – volume: 16 start-page: 323 year: 2010 ident: 10.1016/j.clinthera.2014.09.013_bib10 article-title: Cognitive improvement by activation of alpha7 nicotinic acetylcholine receptors: from animal models to human pathophysiology publication-title: Curr Pharm Des doi: 10.2174/138161210790170094 – volume: 69 start-page: 12 year: 2011 ident: 10.1016/j.clinthera.2014.09.013_bib21 article-title: Immediate and sustained improvements in working memory after selective stimulation of α7 nicotinic acetylcholine receptors publication-title: Biol Psychiatry doi: 10.1016/j.biopsych.2010.08.006 – volume: 29 start-page: 1378 year: 2004 ident: 10.1016/j.clinthera.2014.09.013_bib2 article-title: Effect of nicotine on cognitive deficits in schizophrenia publication-title: Neuropsychopharmacology doi: 10.1038/sj.npp.1300450 – volume: 15 start-page: 1221 year: 2005 ident: 10.1016/j.clinthera.2014.09.013_bib13 article-title: Nicotinic acetylcholine receptor ligands as potential therapeutics publication-title: Exp Opin Ther Patents doi: 10.1517/13543776.15.9.1221 – volume: 32 start-page: 17 year: 2007 ident: 10.1016/j.clinthera.2014.09.013_bib22 article-title: SSR180711, a novel selective α7 nicotinic receptor partial agonist: (II) Efficacy in experimental models predictive of activity against cognitive symptoms of schizophrenia publication-title: Neuropsychopharmacology doi: 10.1038/sj.npp.1301188 – volume: 47 start-page: 211 year: 1974 ident: 10.1016/j.clinthera.2014.09.013_bib29 article-title: The use of analogue scales in rating subjective feelings publication-title: Br J Med Psychol doi: 10.1111/j.2044-8341.1974.tb02285.x – volume: 122 start-page: 302 year: 2009 ident: 10.1016/j.clinthera.2014.09.013_bib11 article-title: A cog in cognition: how the alpha 7 nicotinic acetylcholine receptor is geared towards improving cognitive deficits publication-title: Pharmacol Ther doi: 10.1016/j.pharmthera.2009.03.009 – volume: 52 start-page: 99 year: 2005 ident: 10.1016/j.clinthera.2014.09.013_bib32 article-title: The functional significance of Theta and Upper Alpha oscillations publication-title: Exp Psychol doi: 10.1027/1618-3169.52.2.99 – volume: 11 start-page: 190 year: 1999 ident: 10.1016/j.clinthera.2014.09.013_bib42 article-title: Conventional and quantitative electroencephalography in psychiatry publication-title: J Neuropsychiatry Clin Neurosci doi: 10.1176/jnp.11.2.190 – volume: 583 start-page: 2 year: 2004 ident: 10.1016/j.clinthera.2014.09.013_bib17 article-title: SSR180711A, a novel selective α7 nicotine receptor partial agonist II effects in models predictive of therapeutic activity on cognitive symptoms of Alzheimer’s Disease publication-title: Soc Neurosci – volume: 43 start-page: 273 year: 2001 ident: 10.1016/j.clinthera.2014.09.013_bib35 article-title: Short-term Rivastigmine treatment reduces EEG slow-wave power in Alzheimer patients publication-title: Pharmacoelectroencephalography |
| SSID | ssj0003952 |
| Score | 2.3469644 |
| Snippet | Encenicline (EVP-6124) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in Alzheimer’s disease and... Abstract Purpose Encenicline (EVP-6124) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in... Encenicline (EVP-6124) is a selective α7 nicotinic acetylcholine receptor partial agonist being developed for cognitive impairment in Alzheimer's disease and... |
| SourceID | proquest pubmed crossref elsevier |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 311 |
| SubjectTerms | Administration, Oral Adult bioavailability Biological Availability Capsules Cognition - drug effects Cross-Over Studies Double-Blind Method encenicline cognition Fasting Female Food-Drug Interactions Healthy Volunteers Humans Internal Medicine Male Medical Education Nicotinic Agonists - administration & dosage Nicotinic Agonists - adverse effects Nicotinic Agonists - pharmacokinetics pharmacodynamics pharmacokinetic profile Quinuclidines - administration & dosage Quinuclidines - adverse effects Quinuclidines - pharmacokinetics Receptors, Nicotinic Sex Factors Therapeutic Equivalency Thiophenes - administration & dosage Thiophenes - adverse effects Thiophenes - pharmacokinetics α7 nicotinic acetylcholine receptor agonist |
| Title | Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of Encenicline, a Selective α7 Nicotinic Receptor Partial Agonist, in Single Ascending-dose and Bioavailability Studies |
| URI | https://www.clinicalkey.com/#!/content/1-s2.0-S0149291814006055 https://www.clinicalkey.es/playcontent/1-s2.0-S0149291814006055 https://dx.doi.org/10.1016/j.clinthera.2014.09.013 https://www.ncbi.nlm.nih.gov/pubmed/25438724 https://www.proquest.com/docview/1660412735 |
| Volume | 37 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVESC databaseName: Baden-Württemberg Complete Freedom Collection (Elsevier) customDbUrl: eissn: 1879-114X dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0003952 issn: 0149-2918 databaseCode: GBLVA dateStart: 20110101 isFulltext: true titleUrlDefault: https://www.sciencedirect.com providerName: Elsevier – providerCode: PRVESC databaseName: Elsevier Complete Freedom Collection customDbUrl: eissn: 1879-114X dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0003952 issn: 0149-2918 databaseCode: ACRLP dateStart: 20140101 isFulltext: true titleUrlDefault: https://www.sciencedirect.com providerName: Elsevier – providerCode: PRVESC databaseName: Elsevier SD Freedom Collection customDbUrl: eissn: 1879-114X dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0003952 issn: 0149-2918 databaseCode: .~1 dateStart: 19950101 isFulltext: true titleUrlDefault: https://www.sciencedirect.com providerName: Elsevier – providerCode: PRVESC databaseName: Elsevier SD Freedom Collection Journals [SCFCJ] customDbUrl: eissn: 1879-114X dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0003952 issn: 0149-2918 databaseCode: AIKHN dateStart: 20140101 isFulltext: true titleUrlDefault: https://www.sciencedirect.com providerName: Elsevier – providerCode: PRVLSH databaseName: Elsevier Journals customDbUrl: mediaType: online eissn: 1879-114X dateEnd: 99991231 omitProxy: true ssIdentifier: ssj0003952 issn: 0149-2918 databaseCode: AKRWK dateStart: 19950101 isFulltext: true providerName: Library Specific Holdings – providerCode: PRVPQU databaseName: Health & Medical Collection customDbUrl: eissn: 1879-114X dateEnd: 20250801 omitProxy: true ssIdentifier: ssj0003952 issn: 0149-2918 databaseCode: 7X7 dateStart: 20020101 isFulltext: true titleUrlDefault: https://search.proquest.com/healthcomplete providerName: ProQuest – providerCode: PRVPQU databaseName: ProQuest Central customDbUrl: http://www.proquest.com/pqcentral?accountid=15518 eissn: 1879-114X dateEnd: 20250801 omitProxy: true ssIdentifier: ssj0003952 issn: 0149-2918 databaseCode: BENPR dateStart: 20020101 isFulltext: true titleUrlDefault: https://www.proquest.com/central providerName: ProQuest |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1fa9swEBelhbGXsXb_snZFg9GnePE_Sc7e0pKSbTSEJYW8CduSirdghzod5GXfqQ_7GvtMu7PkhLKVDvZiY6HTCel0d0Z3vyPkXZIwbXgO55snvhcnWeD1E809EIWcM-XDkcIb3YsxH13Gn-ZsvkPO2lwYDKt0ut_q9EZbu5aeW83esih6GJYEtj1AyCYfnHJMNEf0L5Dp9z-2YR5Rv6m6g5097H0nxguzD5s8J4zxsoCnQXSfhbrPA20s0flT8sS5kHRgZ7lPdnR5QB5duEvyA3IysXDU6y6dbbOr6i49oZMtUPX6GfnZfipblh66tC3fYCRLNE2NXsFQaanorFrAeE047ZpWhg5htRBZFzpDBzptauqA-qS_bgVFGVth2iUF11Qv4d-eTnBlcepXFQL2dmlR0inYzoWmA0SVQjvqqarWDbfTokq_p8WiZehCHp-Ty_Ph7GzkuTIOXs6SMPK4gm3PYLJcCWMEiC7LTeinYQwtQZgZcBFEpLIwUIxnWaD9fqoVy3hgwoibLHpBdsuq1K8I9fMEnbxEhCyNRW7SWEcsDhQMykFbqQ7h7dbJ3GGcY6mNhWyD2b7KzZ5L3HPp9yXseYf4G8Klhfl4mCRpZUO2WaygdyWYoodJxd9Ide30Ry0DWYfSl3_IeId82FDeOSb_xvZtK8ISlAjeDKWlrm6AHeeIuyYiYPDSyvZmGRAtARY8fv0_rA_JY_hiNtz9iOyurm_0G_DmVtlxc1zhKebimOwNPn4ejeF9OhxPvvwG_LxQ7g |
| linkProvider | Elsevier |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV3da9swED-6FLa-jK37aPapwehTTPwl2dlbVlrStQmBpNA3YVvS8BbsMKeD_Fl72L-xv2l3tuxSttLBHqPodOLudHdGdz8BvI9jro3I8HyL2HXCOPWcUayFg6aQCa5cPFJ0ozudiclF-OmSX-7AUdsLQ2WV1vc3Pr321nZkaKU5XOf5kMqSMLZ7BNnkYlLO78FuyNEn92B3fHo2mXUOORjVD-_QfIcIbpR5UQNi3epEZV4N5qkX3BakbktC62B08gge2iySjZuNPoYdXezD_am9J9-Hw3mDSL0dsOV1g1U1YIdsfo1VvX0CP9ufqnmZHqe0I19xpYZokRi9waWSQrFlucL16oraLSsNO0aBEbguTsYJbFE_q4MelP36ETEysw11XjLMTvUaP-_ZnIRLW_9cEmbvgOUFW2D4XGk2JmApCqWOKitdc_uYl8n3JF-1DG3V41O4ODleHk0c-5KDk_HYDxyhUPMpblaoyJgIrZdnxncTP8QRz08NZglRoFLfU1ykqafdUaIVT4Vn_ECYNHgGvaIs9AEwN4spz4sjnydhlJkk1AFqXeGiAh2W6oNoVSczC3NOr22sZFvP9kV2Opekc-mOJOq8D25HuG6QPu4miVvbkG0jK7peidHobtLob6S6si6kkp6sfOnKP8y8Dx86yhsn5d_YvmtNWKIfocuhpNDlFbITgqDXogAZPG9suxMDASagwMMX_8P6LTyYLKfn8vx0dvYS9vAf3lS_v4Le5tuVfo3J3SZ9Yw_vb88WURg |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Pharmacodynamics%2C+Pharmacokinetics%2C+Safety%2C+and+Tolerability+of+Encenicline%2C+a+Selective+%CE%B17+Nicotinic+Receptor+Partial+Agonist%2C+in+Single+Ascending-dose+and+Bioavailability+Studies&rft.jtitle=Clinical+therapeutics&rft.au=Barbier%2C+Ann+J.%2C+MD%2C+PhD&rft.au=Hilhorst%2C+Martijn%2C+PhD&rft.au=Vliet%2C+Andr%C3%A9+Van%2C+MD%2C+PhD&rft.au=Snyder%2C+Peter%2C+PhD&rft.date=2015-02-01&rft.issn=0149-2918&rft.volume=37&rft.issue=2&rft.spage=311&rft.epage=324&rft_id=info:doi/10.1016%2Fj.clinthera.2014.09.013&rft.externalDBID=ECK1-s2.0-S0149291814006055&rft.externalDocID=1_s2_0_S0149291814006055 |
| thumbnail_m | http://utb.summon.serialssolutions.com/2.0.0/image/custom?url=https%3A%2F%2Fcdn.clinicalkey.com%2Fck-thumbnails%2F01492918%2FS0149291814X00135%2Fcov150h.gif |