Yamamura M, Nakagawa H, Kinoshita K, Ochiai T, Ishida R
Pharmacology Department, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Jpn J Pharmacol. 1988 Oct;48(2):203-12. doi: 10.1254/jjp.48.203.
Behavioral pharmacological studies on mafoprazine, a new drug for the prevention of aggressive behavior, were performed to compare its effects with those of an existing drug, azaperone (Stresnil). The acute toxicity of mafoprazine in mice was slightly stronger than that of azaperone. Mafoprazine showed the following effects (at 0.2 to 2.0 mg/kg, s.c.): a decrease in spontaneous motor activity, prolongation of the duration of pentobarbital anesthesia, inhibition of long-term isolation-induced aggressive behavior, inhibition of olfactory bulbectomy-induced hyperemotionality and muricide behavior in mice and rats, and a marked taming and tranquilizing effect on aggressive behavior in dogs. These effects of mafoprazine were qualitatively the same as those of azaperone. Mafoprazine showed cataleptogenicity in rats at 5 mg/kg, s.c. or more and motor incoordination in rats at 0.2 mg/kg, s.c. or more. In the experiment on operant behavior in rats, the effect of mafoprazine on differential reinforcement of the low rate (DRL) response was almost the same as those of azaperone and chlorpromazine. These results indicate that mafoprazine has substantially the same psychotropic effect as azaperone, while the former has a weaker action on the extrapyramidal system than the latter, suggesting that mafoprazine could be used as a unique aggression-inhibiting drug.
对预防攻击行为的新药吗氯贝胺进行了行为药理学研究,以将其效果与现有药物阿扎哌隆(Stresnil)的效果进行比较。吗氯贝胺对小鼠的急性毒性略强于阿扎哌隆。吗氯贝胺(皮下注射,剂量为0.2至2.0mg/kg)显示出以下效果:自发运动活动减少、戊巴比妥麻醉持续时间延长、抑制长期隔离诱导的攻击行为、抑制小鼠和大鼠嗅球切除诱导的过度情绪化和杀鼠行为,以及对犬类攻击行为有明显的驯服和镇静作用。吗氯贝胺的这些效果在性质上与阿扎哌隆相同。吗氯贝胺皮下注射5mg/kg及以上剂量时在大鼠中显示出僵住作用,皮下注射0.2mg/kg及以上剂量时在大鼠中显示出运动不协调。在大鼠的操作性行为实验中,吗氯贝胺对低速率(DRL)反应的差异强化作用与阿扎哌隆和氯丙嗪的作用几乎相同。这些结果表明,吗氯贝胺与阿扎哌隆具有基本相同的精神otropic作用,而前者对外周锥体外系的作用比后者弱,这表明吗氯贝胺可作为一种独特的攻击抑制药物使用。