Pregabalin: as adjunctive treatment of partial seizures.
Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methylhexanoic acid, possesses anticonvulsant activity. Pregabalin binds with high affinity and specificity to voltage-gated calcium channel alpha(2)-delta proteins. The putative mechanism of action of the drug is reduced excitatory neurotransmitter release caused by binding to the alpha(2)-delta protein, resulting in allosteric modulation of P/Q-type voltage-gated calcium channels. In three well designed trials, oral pregabalin as adjunctive therapy in patients with refractory partial seizures was significantly (p < or = 0.0007) more effective than placebo in reducing seizure frequency when administered at dosages of 150-600 mg/day (as two or three divided doses). Adjunctive pregabalin produced an overall mean 41.3% improvement from baseline in 28-day seizure-free rate in four long-term (maximum exposure 1764 days), open-label studies in 1480 patients. CNS-related effects (e.g. dizziness and somnolence) were the most frequent dose-related treatment-emergent adverse events associated with adjunctive pregabalin therapy.
Warner
Greg
G
Adis International Limited, Auckland 1311, New Zealand.
Figgitt
David P
DP
D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D017277:Drug Approval; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005062:European Union; D006801:Humans; D000069583:Pregabalin; D014481:United States; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid
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