Dissimilar effects of nicotinamide and inosine, putative endogenous ligands of the benzodiazepine receptors, on pentylenetetrazol seizures in four strains of mice.

In adult male albino BALB/c mice inosine (INS, 100 and 200 micrograms, intraventricularly) prolonged the latency of pentylenetetrazol (PTZ) seizures while nicotinamide (NAM) exerted an opposite effect. In adult male C57BL/6 mice INS decreased lethality after PTZ while NAM increased it. In adult male albino SHR (bred from Swiss) and in adult male CC57BR mice INS and NAM did not modify the effect of PTZ. Both INS and NAM administered ICB induced short-lasting locomotor excitement in albino SHR and BALB/c mice but not in C57BL/6 or CC57BR mice. Pretreatment with INS (300 mg/kg, IP) prolonged the latency of PTZ seizures only in SHR mice. Pretreatment with NAM was ineffective in all strains tested. Chronic treatment with NAM and INS (100 mg/kg, IP, daily for 5 days) in SHR mice did not modify the effect of PTZ. The data obtained emphasize the importance of the appropriate choice of mouse strain for studies on INS and NAM as puntative endogenous ligands of the BDZ receptor (BDZR). The opposite effects of INS and NAM raise doubts that these two substances could play the same or similar roles in the function of a type of BDZR which is related to the action of PTZ on the central nervous system.