A microdialysis study on the mechanism of action of gabapentin.
To gain insight into the mechanism of action of the anti-epileptic, gabapentin, the effects of gabapentin on the in vivo extracellular gamma-aminobutyric acid (GABA) levels in the rat substantia nigra reticulata were studied using microdialysis. In order to investigate possible interference with different GABA-ergic compartments in the substantia nigra reticulata, we studied the effects of gabapentin under basal, K(+)-, nipecotic acid- and glutamate-stimulated conditions. Intraperitoneally (i.p.) administered gabapentin, at a dose of 100 mg/kg, did not significantly affect extracellular GABA levels under any condition. Thus, our data do not support the involvement of nigral GABA release in the mechanism of action of the anti-epileptic gabapentin.
Timmerman
W
W
Department of Medicinal Chemistry, University Center for Pharmacy, Ant. Deusinglaan 1, 9713 AV, Groningen, The Netherlands. wia@farm.rug.nl
Bouma
M
M
De Vries
J B
JB
Davis
M
M
Westerink
B H
BH
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids; D000077206:Gabapentin; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009557:Nipecotic Acids / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D009557:Nipecotic Acids; C030278:nipecotic acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D011392:Proline; C010983:homoproline; D011188:Potassium