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.
Gomita
Y
Y
Department of Hospital Pharmacy, Okayama University Medical School, Japan.
Ichimaru
Y
Y
Moriyama
M
M
Furuno
K
K
Suemaru
K
K
Osman
F E
FE
Araki
Y
Y
D000777:Anesthetics; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009125:Muscle Relaxants, Central; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects
D000777:Anesthetics; D007211:Indoles; D009125:Muscle Relaxants, Central; D008694:Methamphetamine; C063836:tepirindole