1965 年 85 巻 8 号 p. 715-719
The analgesic activities of 1, 4-bis (phenoxyacetyl) piperazine and its derivatives substituted with various groups in both phenyl groups were tested in mice by the pressure method. At the same time, the effect of these compounds on climbing test (measured by Sandberg's method) and barbital anesthesia in mice was studied.
In regard to analgesic action, the following results were obtained. When the phenyl rings were substituted with one alkyl, methyl- and propyl-substituted compounds showed a potent activity, but action of ethyl substituted one was very weak. Among methoxyl-substituted derivatives, specific depression of analgesic activity was observed when methoxyl was substituted in the ortho position in the phenyl ring. No analgesic action was observed in hydroxy-substituted compounds. When two groups were substituted in both phenyl rings, only the following three compounds showed analgesic actions: 2-methoxy-4-allyl, 2-methoxy-4-propyl, and 2-methoxy-4-ethoxycarbonyl derivatives. When a halogen was substituted in phenyl rings, only the monochloro derivatives showed analgesic activity, and this activity was not influenced by the position of chlorine in the phenyl rings.
Potent depressing activities of climbing in mice were observed only in o-chloro and o-bromo derivatives, and activities of other compounds were very weak. The compounds which showed inhibitory action on climbing response generally possessed prolonging action on barbital anesthesia.
The climbing inhibiting actions of AP-38 and AP-41 were more potent when these were injected intraperitoneally, and activities were depressed extremely by oral treatment.