Pregabalin: From molecule to medicine.
Pregabalin, a compound with a novel mechanism of action (MOA), has demonstrated efficacy as an adjunctive treatment for epilepsy and in several neuropathic pain models. Multiple generalized anxiety disorder (GAD) clinical trials have shown that pregabalin has efficacy similar to the benzodiazepines and venlafaxine. Onset of anxiolytic effect was observed as early as Week 1 of treatment, and efficacy was seen in treating both psychic and somatic anxiety symptoms. Pregabalin binds potently and selectively to the alpha-2-delta subunit of "hyper-excited" voltage-gated calcium channels (VGCCs). The binding of pregabalin to VGCCs changes their conformation, reducing calcium influx at nerve terminals. Pregabalin only modulates the release of excitatory neurotransmitters in "hyper-excited" neurons, restoring them to normal physiological state. This newly defined MOA is believed to confer on pregabalin its anxiolytic, analgesic, and anticonvulsant properties. Thus, pregabalin may offer physicians an effective and well-tolerated therapy for GAD, which differs from existing treatments.
Kavoussi
Richard
R
Pfizer Global Research and Development, Ann Arbor, MI 48105, USA. Richard.Kavoussi@pfizer.com
D000379:Agoraphobia / Q000188:drug therapy*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D010146:Pain / Q000188:drug therapy; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D014151:Anti-Anxiety Agents; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid