Effect of lamotrigine on the electrically-evoked release of endogenous amino acids from slices of dorsal horn of the rat spinal cord.
The novel anti-epileptic, lamotrigine (LTG) has been shown to exhibit antinociceptive effects in the rat. In the present study, the effect of LTG on the electrically-evoked release of endogenous amino acids from rat isolated spinal dorsal horn slices with intact dorsal roots has been examined and compared with those of morphine in the same preparation. LTG (0.1-300 microM) inhibited the release of aspartate, glutamate and GABA in a concentration-dependent manner. The lowest concentrations of morphine (0.001-0.01 microM) enhanced the stimulated release of aspartate and glutamate while the higher concentrations inhibited their release. Stimulated GABA release was reduced in a concentration-dependent manner. The anticonvulsant was more potent at inhibiting the release of glutamate (IC50 = 20 microM) than that of GABA (IC50 = 44 microM) supporting the previous suggestion that lamotrigine is a selective inhibitor of glutamate release. This suggests that the reduction in glutamate release could be one of the mechanisms by which lamotrigine exerts its antinociceptive effect.
Teoh
H
H
Department of Pharmacology, School of Pharmacy, London, U.K.
Fowler
L J
LJ
Bowery
N G
NG
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001224:Aspartic Acid / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D000077213:Lamotrigine; D008297:Male; D009020:Morphine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D014227:Triazines / Q000494:pharmacology*
D000596:Amino Acids; D000927:Anticonvulsants; D014227:Triazines; D001224:Aspartic Acid; D018698:Glutamic Acid; D009020:Morphine; D000077213:Lamotrigine