Nicotinamide, inosine and hypoxanthine, putative endogenous ligands of the benzodiazepine receptor, opposite to diazepam are much more effective against kynurenine-induced seizures than against pentylenetetrazol-induced seizures.
Nicotinamide (NAM, 1000 mg/kg), inosine (INS, 1000 mg/kg), hypoxanthine (HXT, 500 mg/kg), putative endogenous ligands of the benzodiazepine receptor, and nicotinic acid (NA, 500 mg/kg) diminished DL-kynurenine-(DL-K, 50 micrograms ICV) induced seizures in C57BL/6 adult male mice and only prolonged the latency of pentylenetetrazol (PTZ, 500 micrograms iCV) seizures. The same effect was previously observed when PTZ was administered IP. In albino male BALB/c and SHR (bred from Swiss) mice only NA was effective against DL-K. Diazepam in a dose of 0.5 mg/kg prevented PTZ-induced seizures in half of the animals but even in dose of 10 and 20 mg/kg it was ineffective against DL-K. When injected ICV NAM (1 and 10 micrograms), INS (10 micrograms) and HXT (10 micrograms) prevented seizures induced by DL-K and were ineffective against seizures induced by PTZ. It is suggested that if NAM, INS and HXT are of functional importance in the central nervous system, they can act as antagonists of endogenous brain kynurenine. NA and NAM are suggested to be functional feedback inhibitory regulators of the kynurenine pathway of metabolism of tryptophan.
D000818:Animals; D000927:Anticonvulsants; D001667:Binding, Competitive; D003975:Diazepam / Q000494:pharmacology; D007042:Hypoxanthines / Q000494:pharmacology*; D007288:Inosine / Q000494:pharmacology*; D007737:Kynurenine / Q000037:antagonists & inhibitors; D008024:Ligands; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009536:Niacinamide / Q000494:pharmacology*; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D012640:Seizures / Q000139:chemically induced
D000927:Anticonvulsants; D007042:Hypoxanthines; D008024:Ligands; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D009536:Niacinamide; D007737:Kynurenine; D007288:Inosine; D003975:Diazepam; D010433:Pentylenetetrazole