A behavioral pharmacological study of mafoprazine, a new phenylpiperazine derivative

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.