Centrally Acting Muscle Relaxant Activities of 2-Methyl-3-pyrrolidinopropiophenone Derivatives

• Published in: YAKUGAKU ZASSHI Vol. 107; no. 9; pp. 705 - 710
• Main Authors: YAMAZAKI, MITSUO, AOKI, YASUJI, KATO, HIDEO, ITO, YASUO, KONTANI, HITOSHI, KOSHIURA, RYOZO
• Format: Journal Article
• Language: Japanese; English
• Published: The Pharmaceutical Society of Japan 25.09.1987
• Subjects: 2-methyl-3-pyrrolidinopropiophenone; anemic decerebrate rigidity; anticonvulsant activity; centrally acting muscle relaxant activity; hexobarbital sleeping time; phenyl group p-substituent; rotating rod; structure-activity relationship; toxicity
• ISSN: 0031-6903; 1347-5231
• DOI: 10.1248/yakushi1947.107.9_705

The compounds of 2-methyl-3-pyrrolidinopropiophenone structure, in which the p-position of phenyl group is hydrogen, alkyl group (C1-C4), cyclohexyl group or fluoromethyl group, were synthesized and the centrally acting muscle relaxant activities of these compounds were studied after peroral or intraduodenal administration. On the muscle relaxant activity in rotating rod method in mice, compound which contains ethyl, n-propyl, isopropyl or n-butyl group had almost equipotent inhibitory activity, but the inhibitory effect on the anemic decerebrate rigidity in rats of ethyl substituent compound was stronger than other compounds. The muscle relaxant activities of the compound containing cyclohexyl or fluoromethyl group were weaker than those of other compounds. The hexobarbital induced sleeping time was more prolonged by the compound containing hydrogen or butyl group at p-position. Toxicities (body weight decrease or mortality) in mice and rats were potentiated according to the length of alkyl chain. These results suggested that ethyl group would be suitable for the p-substituent of phenyl group of the compounds as a centrally acting muscle relaxant. The pyrroridinopropiophenone derivatives had stronger inhibitory effect on convulsion induced by nicotine, as compared with the piperidinopropiophenone analoges.