[Central muscle relaxant activities of 2-methyl-3-aminopropiophenone derivatives]

Nihon Yakurigaku Zasshi. 1987 Feb;89(2):91-101. doi: 10.1254/fpj.89.91.
[Article in Japanese]

Abstract

In this experiment, we synthetized new 2-methyl-3-aminopropiophenone (MP) derivatives, whose structure is known to have central muscle relaxant activities, and quinolizidine and indan . tetralin derivatives derived from MP by cyclization, and we investigated the central muscle relaxant activity. Among the quinolizidine derivatives, there was a very strong central depressant agent, trans (3H, 9aH)-3-(p-chloro) benzoyl-quinolizidine (HSR-740), and among the indan . tetralin derivatives, there was an excitant agents, trans (1H, 2H)-5-methoxy-3, 3-dimethyl-2-piperidinomethyl indan-1-ol (HSR-719). From the results, these derivatives were not considered to be adequate for central muscle relaxant. Among the MP derivatives, (4'-chloro-2'-methoxy-3-piperidino) propiophenone HCl (HSR-733) and (4'-ethyl-2-methyl-3-pyrrolidino) propiophenone HCl (HSR-770) strongly inhibited the cooperative movement in the rotating rod method using mice, and it exerted almost the same depressant activity on the cross extensor reflex using alpha-chloralose anesthetized rats. However, the inhibitory effects of HSR-733 on the anemic decerebrate rigidity and the rigidity induced by intracollicular decerebration in rats were weaker than those of HSR-770 and eperisone. In spinal cats, at a low dose (5 mg/kg, i.v.), HSR-733 depressed monosynaptic and dorsal root reflex potentials as compared with polysynaptic reflex potentials, and inhibitory effects of HSR-733 on these three reflex potentials were more potent than those of eperisone and HSR-770. Although HSR-770 acts on the spinal cord and supraspinal level on which eperisone has been reported to act, HSR-733 may mainly act on the spinal cord. These results indicate that the MP derivative with a 2-methyl group may be suitable as a central muscle relaxant. HSR-770, which has equipotent muscle relaxant activity to eperisone, exerted strong inhibitory effects on oxotremorine-induced tremor and weak inhibitory effects on spontaneous motor activity in the Animex method using mice, as compared with eperisone.

Publication types

  • Comparative Study
  • English Abstract

MeSH terms

  • Animals
  • Cats
  • Mice
  • Muscle Relaxants, Central / chemical synthesis*
  • Muscle Relaxants, Central / pharmacology
  • Piperidines / chemical synthesis*
  • Piperidines / pharmacology
  • Propiophenones / chemical synthesis*
  • Propiophenones / pharmacology
  • Quinolizines / chemical synthesis*
  • Quinolizines / pharmacology
  • Rats

Substances

  • Muscle Relaxants, Central
  • Piperidines
  • Propiophenones
  • Quinolizines
  • inaperisone
  • trans(1H,2H)-5-methoxy-3,3-dimethyl-2-piperidinomethylindan-1-ol hydrochloride
  • eperisone
  • HSR 740
  • (4'-chloro-2'-methoxy-3-piperidino)propiophenone hydrochloride