Toide K, Murakami H, Miyake H
Section of Pharmacology, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Yakubutsu Seishin Kodo. 1989 Jun;9(2):233-40.
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.
由于抗尿频药物盐酸丙哌维林(P-4)在一般药理学实验中增加了小鼠的自发运动活性,因此通过小鼠和大鼠的自发运动活性实验、惊厥诱导作用实验以及低比率差异强化(DRL)实验,进一步研究了P-4的行为药理学效应。高剂量的P-4(100mg/kg,口服)可轻微但显著提高大鼠的自发运动活性水平。P-4(10、20和50mg/kg,口服,持续一周)对小鼠的活性水平没有影响,而甲基苯丙胺在以1mg/kg的剂量皮下注射给药一周后会产生反向耐受性。P-4(20、50和100mg/kg,口服)与低于小鼠阈值的戊四氮剂量(40mg/kg,腹腔注射)联合使用时,不会诱发惊厥行为,如最小完全惊厥(M.F.S.)、阵挛性惊厥(C.C.)和强直性惊厥(T.C.),而甲基苯丙胺(8mg/kg,皮下注射)与戊四氮联合使用会诱发M.F.S.。在大鼠食物强化的DRL实验中,P-4(50和100mg/kg,口服)降低了强化率,但不影响其他参数。另一方面,甲基苯丙胺(0.5、1和2mg/kg,皮下注射)以剂量依赖的方式促进了DRL反应,并分别降低了强化率、平均反应间隔时间和效率。这些结果表明,P-4不具有类似甲基苯丙胺的中枢神经系统刺激作用。