Behavioral effects of HR-592, a new derivative of indole

Effects of HR-592 on various behaviors were investigated in rats and mice. 1) HR-592 at doses of 10-100 mg/kg, p.o., and chlorpromazine at doses of 2.5-20 mg/kg, p.o., suppressed dose-dependently spontaneous activities of mice. 2) In the mice treated with HR-592, 10 and 30 mg/kg, p.o., and with chlorpromazine, 1.25-5 mg/kg, p.o., the durations of loss of the righting reflex induced by thiopental-Na were extended in a dose-dependent manner. 3) In the mice and rats when HR-592 was administered at doses of 3-100 mg/kg, p.o., catalepsy was induced in a dose-dependent manner. 4) The incidence of catalepsy induced by haloperidol in mice was reduced dose-dependently after HR-592 administration (10-100 mg/kg, p.o.). 5) Dose-dependent suppressions of the slant of screen at which the mice slipped down were observed by HR-592 at 3-100 mg/kg, p.o., and chlorpromazine at 5-20 mg/kg, p.o. 6) The rotarod performance in mice was suppressed dose-dependently by HR-592, 3-100 mg/kg, p.o., and chlorpromazine, 5-20 mg/kg, p.o. 7) HR-592 at doses of 0.3-3 mg/kg, i.p., suppressed dose-dependently the turning behavior induced by methamphetamine in unilateral substantia nigra-lesioned rats. From these results and our previous data, it is considered that HR-592 has pharmacological properties as a major tranquilizer, although its behavioral effect is slightly weaker than that of chlorpromazine. Furthermore, these results imply that HR-592 has anti-cataleptogenic activity and might thereby alleviate the adverse effect of neuroleptics such as haloperidol.