Gabapentin decreases monoamine release without affecting acetylcholine release in the brain.
Superfused rat brain cortex slices preincubated with 3H-noradrenaline or 3H-serotonin and superfused rabbit caudate nucleus slices preincubated with 3H-choline were used to examine the effects of gabapentin (an amino acid chemically related to gamma-aminobutyric acid, GABA) on the electrically evoked 3H overflow. Gabapentin inhibited the electrically (3 Hz) evoked 3H overflow from slices preincubated with the 3H-monoamines in a concentration-dependent manner (at 1 mmol/l by 20-30%), but did not affect the evoked overflow from slices preincubated with 3H-choline. The following drugs did not modify the inhibitory effects of gabapentin: bicuculline, RS-baclofen, GABA, phentolamine, metitepin, cocaine, and the inhibitor of serotonin uptake, 6-nitroquipazine. Gabapentin did not modify the inhibitory effect of GABA on the evoked 3H overflow from slices preincubated with 3H-serotonin. In slices preincubated with 3H-noradrenaline the inhibitory effect of gabapentin was still observed when the stimulation frequency was 10 instead of 3 Hz. In conclusion, gabapentin mimics GABAB receptor activation, but it appears to act by a GABA receptor-independent, as yet unidentified mechanism.
D000085:Acetates / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism*; D000588:Amines; D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects*; D003509:Cyclohexanecarboxylic Acids; D004558:Electric Stimulation; D005260:Female; D000077206:Gabapentin; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000109:Acetylcholine; D009638:Norepinephrine