The inhibitory effect of endogenous convulsants quinolinic acid and kynurenine on the pentobarbital stimulation of [3H]flunitrazepam binding.

The metabolites of tryptophan-kynurenines with convulsant action quinolinic acid (QA) and l-kynurenine (l-KYN) antagonized the enhancing effect of pentobarbital (1 mM) on [3H]Flunitrazepam binding. IC50 for l-KYN were 35.9 +/- 14.8 microM and for QA 31.2 +/- 7.2 microM respectively. The inhibitory effect of KYN was stereoselective: IC50 of l-isomer was about two fold lower than IC50 of racemic form, d,l-KYN. Scatchard analysis revealed that inhibitory effect of QA and l-KYN on [3H]Flunitrazepam binding enhanced by pentobarbital is due to the decrease in affinity of benzodiazepine receptors. On the basis of these data it is proposed that QA and l-KYN possess their convulsant action interacting with barbiturate/picrotoxin sensitive sites of GABA-benzodiazepine-barbiturate complex.