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[Behavioral pharmacological properties of propiverine hydrochloride (P-4) in mice and rats]
K Toide1, H Murakami, H Miyake
1Section of Pharmacology, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Abstract:
Since propiverine hydrochloride (P-4), an anti-pollakiuria drug, increased the spontaneous motor activity of mice in general pharmacological experiments, behavioral pharmacological effects of P-4 were further studied by experiments for spontaneous motor activity, convulsion-inducing effect, and differential reinforcement of low rate (DRL) schedule in mice and rats. A high dose of P-4 (100 mg/kg, p.o.) increased slightly but significantly the spontaneous motor activity level in rats. P-4 (10, 20, and 50 mg/kg, p.o. for one week) did not affect the activity level in mice, whereas methamphetamine caused the reverse tolerance after being daily administered for one week at a dose of 1 mg/kg, s.c. P-4 (20, 50, and 100 mg/kg, p.o.) did not induce convulsive behaviors such as minimal full seisure (M.F.S.), clonic convulsion (C.C.) and tonic convulsion (T.C.) in combination with a dose (40 mg/kg, i.p.) of pentylenetetrazol, which is below the threshold in mice, whereas methamphetamine (8 mg/kg, s.c.) in combination with pentylenetetrazol induced M.F.S. Under a DRL schedule for food reinforcement in rats, P-4 (50 and 100 mg/kg, p.o.) lowered the reinforcement rate, but it did not affect other parameters. On the other hand, methamphetamine (0.5, 1, and 2 mg/kg, s.c.) facilitated DRL responses and lowered the reinforcement rate, mean of inter-response time, efficiency, respectively, in a dose-dependent manner. These results suggest that P-4 does not possess the methamphetamine-like CNS stimulating effect.