Effects of clobenpropit (VUF-9153), a histamine H3-receptor antagonist, on learning and memory, and on cholinergic and monoaminergic systems in mice.

The effects of clobenpropit (VUF-9153), a potent histamine H3-receptor antagonist, on a scopolamine-induced learning deficit in the step-through passive avoidance test was studied in mice. Clobenpropit (10 and 20 mg/kg) alone showed a tendency to ameliorate the scopolamine-induced learning deficit, and clobenpropit (10 mg/kg) in combination with zolantidine (20 mg/kg), a histamine H2-receptor antagonist, ameliorated the scopolamine-induced effect. This ameliorating effect was antagonized by (R)-alpha-methylhistamine (20 mg/kg), a histamine H3-receptor agonist and pyrilamine (20 mg/kg), a histamine H1-receptor antagonist, suggesting that clobenpropit in combination with zolantidine showed the ameliorating effect via histamine H3 receptors and/or histamine H1 receptors. We also studied the effects of clobenpropit on cholinergic and monoaminergic systems. Clobenpropit did not show any significant effect on these neuronal systems except the activation of noradrenergic system. The present results suggest that the effect of clobenpropit might be partially involved with the activation of noradrenergic system, and the histaminergic system may play certain important roles in learning and memory.