Methohexitone antagonises kainate and epileptiform activity in rat neocortical slices.
Using a grease-seal technique on cortical slices, methohexitone (10-316 microM) dose dependently and reversibly reduced depolarising responses to kainate more than those to alpha-amino-3-hydroxy-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA). The respective pA2 values were 4.9 +/- 0.07, 3.6 +/- 0.03 and 4.0 +/- 0.05 whereas, for 6-nitro,7-sulphamoylbenz[F]quinoxalinedione (NBQX), they were 5.8 +/- 0.06, 6.7 +/- 0.05 and < 4.0. Methohexitone was also more effective than NBQX in reducing the spontaneous epileptiform activity occurring in these cortical slices. Thus 10 and 20 microM of this short-acting barbiturate reduced afterpotentials and burst frequencies respectively by about 50% whereas NBQX 10 microM only reduced burst frequency by some 15%. The results are discussed with respect to a putative methohexitone- and kainate-sensitive autoreceptor which facilitates presynaptic glutamate release.
Palmer
A J
AJ
Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK.
Zeman
S
S
Lodge
D
D
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000503:physiopathology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000037:antagonists & inhibitors*; D008723:Methohexital / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects; D018092:Kainic Acid Receptors; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D007608:Kainic Acid; D008723:Methohexital; D011810:Quinoxalines; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D005680:gamma-Aminobutyric Acid; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline