The mechanisms of action of gabapentin and pregabalin.
Gabapentin and pregabalin are structurally related compounds with recognized efficacy in the treatment of both epilepsy and neuropathic pain. The pharmacological mechanisms by which these agents exert their clinical effects have, until recently, remained unclear. The interaction of gabapentin and pregabalin with conventional antiepileptic and analgesic drug targets is likely to be modest, at best, and has been largely dismissed in favour of a selective inhibitory effect on voltage-gated calcium channels containing the alpha2delta-1 subunit. This mechanism is consistently observed in both rodent- and human-based experimental paradigms and may be sufficiently robust to account for much of the clinical activity of these compounds.
Sills
Graeme J
GJ
Epilepsy Unit Division of Cardiovascular & Medical Sciences, Western Infirmary, Glasgow G11 6NT, Scotland. g.j.sills@clinmed.gla.ac.uk
D000588:Amines / Q000494:pharmacology*; D026905:Amino Acid Transport Systems / Q000187:drug effects / Q000378:metabolism; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D000077206:Gabapentin; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D000069583:Pregabalin; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000588:Amines; D026905:Amino Acid Transport Systems; D000700:Analgesics; D000927:Anticonvulsants; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D018080:Receptors, GABA-B; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin