Pregabalin Exerts Oppositional Effects on Different Inhibitory Circuits in Human Motor Cortex: A Double‐blind, Placebo‐controlled Transcranial Magnetic Stimulation Study

• Published in: Epilepsia (Copenhagen) Vol. 47; no. 5; pp. 813 - 819
• Main Authors: Lang, Nicolas, Sueske, Elke, Hasan, Alkomiet, Paulus, Walter, Tergau, Frithjof
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.05.2006; Blackwell
• Subjects: Adult; Amines - pharmacology; Anticonvulsants - pharmacology; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Calcium Channels - drug effects; Calcium Channels - physiology; Cyclohexanecarboxylic Acids - pharmacology; Double-Blind Method; Evoked Potentials, Motor - drug effects; Evoked Potentials, Motor - physiology; Female; GABA; gamma-Aminobutyric Acid - analogs & derivatives; gamma-Aminobutyric Acid - pharmacology; gamma-Aminobutyric Acid - physiology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Intracortical inhibition; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Motor Cortex - drug effects; Motor Cortex - physiology; Nervous system; Nervous system (semeiology, syndromes); Neural Inhibition - drug effects; Neural Inhibition - physiology; Neurology; Neuropharmacology; Neurotransmitter Uptake Inhibitors - pharmacology; Nipecotic Acids - pharmacology; Pharmacology. Drug treatments; Placebos; Pregabalin; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Receptors, GABA-B - drug effects; Receptors, GABA-B - physiology; Recruitment, Neurophysiological - drug effects; Recruitment, Neurophysiological - physiology; Silent period; Transcranial magnetic stimulation; Transcranial Magnetic Stimulation - statistics & numerical data; Voltage‐dependent calcium channel; Human; Nervous system diseases; Transcranial magnetic stimulation; Motor pathway; Calcium; Epilepsy; Central nervous system; Anticonvulsant; Pregabalin; Inorganic element; Cerebral disorder; Analgesic; Motor cortex; Central nervous system disease; Voltage; Neurotransmitter; GABA; Pregabalin-Transcranial magnetic stimulation-Intracortical inhibition-Silent period-GABA- Voltage-dependent calcium channel
• ISSN: 0013-9580; 1528-1157; 1528-1167; 1528-1167
• DOI: 10.1111/j.1528-1167.2006.00544.x

Purpose: To explore acute effects of pregabalin (PGB) on human motor cortex excitability with transcranial magnetic stimulation (TMS).  Methods: PGB, 600 mg/day, was orally administered in 19 healthy subjects twice daily in a randomized, double‐blind, placebo‐controlled crossover design. Several measures of motor cortex excitability were tested with single‐ and paired‐pulse TMS.  Results: Mean short‐interval intracortical inhibition (SICI) was reduced after PGB (74 ± 7% of unconditioned response) compared with placebo (60 ± 6% of unconditioned response). In contrast, mean long‐interval intracortical inhibition (LICI) was increased by PGB (26 ± 4% of unconditioned response) compared with placebo (45 ± 8% of unconditioned response), and mean cortical silent period (CSP) showed an increase from 139 ± 8 ms or 145 ± 8 ms after placebo to 162 ± 7 ms or 161 ± 10 ms after PGB. Motor thresholds, intracortical facilitation, and corticospinal excitability were unaffected.  Conclusions: The observed excitability changes with oppositional effects on SICI and LICI or CSP suggest γ‐aminobutyric acid (GABA)B‐receptor activation. They are markedly distinct from those induced by gabapentin, although both PGB and gabapentin are thought to mediate their function by binding to the α(2)‐δ subunit of voltage‐gated calcium channels. Conversely, the TMS profile of PGB shows striking similarities with the pattern evoked by the GABA‐reuptake inhibitor tiagabine.