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.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D005479:Flurazepam / Q000378:metabolism*; D007700:Kinetics; D007737:Kynurenine / Q000494:pharmacology*; D008297:Male; D010424:Pentobarbital / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010848:Picolinic Acids / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*
D000927:Anticonvulsants; D010848:Picolinic Acids; D011725:Pyridines; D011805:Quinolinic Acids; D011963:Receptors, GABA-A; D007737:Kynurenine; D017378:Quinolinic Acid; D010424:Pentobarbital; D005479:Flurazepam; C030614:picolinic acid