Cellular and molecular action of the putative GABA-mimetic, gabapentin

• Published in: Cellular and molecular life sciences : CMLS Vol. 60; no. 4; pp. 742 - 750
• Main Authors: Maneuf, Y P, Gonzalez, M I, Sutton, K S, Chung, F Z, Pinnock, R D, Lee, K
• Format: Journal Article
• Language: English
• Published: Switzerland Springer Nature B.V 01-04-2003; Birkhäuser Verlag
• Subjects: Acetates - pharmacology; Amines; Analgesics - pharmacology; Animals; Anticonvulsants - pharmacology; Anxiety - drug therapy; Binding sites; Brain - drug effects; Brain - metabolism; Calcium channels; Cellular biology; Central nervous system; Cyclohexanecarboxylic Acids; Disease Models, Animal; Drugs of the Future: Review; Epilepsy; Gabapentin; gamma-Aminobutyric Acid - drug effects; Humans; Ion Channels - drug effects; Kinases; Molecular biology; Neurotransmitter Agents - metabolism; Pain; Pain - drug therapy; Proteins; Rats; Seizures - drug therapy; Signal Transduction - drug effects
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-003-2108-x

Gabapentin was originally designed as an anti-convulsant gamma-aminobutyric acid (GABA) mimetic capable of crossing the blood-brain barrier. In the present review we show that although gabapentin is not a GABA mimetic, it has great utility as an add-on therapy for epilepsy and as a first-line treatment for neuropathic pain. We summarise the studies that have been performed which demonstrate that gabapentin appears to interact with a novel binding site expressed at high density within the central nervous system (CNS), namely the alpha2delta voltage-dependent calcium channel subunit. The review continues by examining the effects of gabapentin on calcium channel function and neurotransmitter release before, in the latter part of the review, summarising the more recently discovered actions of gabapentin in relation to intracellular signalling.