Pharmacological properties of the new centrally acting muscle relaxant (R)-(+)-3-phenyl-5-[2-(1-pyrrolidinylmethyl)butyryl]isoxazole hydrochloride.
The pharmacological properties of (R)-(+)-3-phenyl-5-[2-(1-pyrrolidinylmethyl)butyryl]isoxazole hydrochloride (CAS 144576-50-1, MS-322), a new centrally acting muscle relaxant, were investigated and compared with those of eperisone-HCl (CAS 56839-43-1) in experimental animals. MS-322 (1.5-6 mg/kg i.v.) reduced both anemic and intercollicular decerebration-induced rigidity in rats. Similar doses were required for these effects. The activity of MS-322 (200 mg/kg p.o.) against intercollicular decerebration-induced rigidity was greater and longer lasting than that of the same dose of eperisone-HCl. MS-322 (0.75-6 mg/ kg i.v.) inhibited the flexor reflex in anesthetized cats in a dose-dependent manner and more strongly than eperisone-HCl. MS-322 had no effect on the neuromuscular junction in anesthetized rats. The muscle relaxant activity of MS-322 in mice, demonstrated by the traction and rota-rod tests was stronger than that of eperisone-HCl, whereas MS-322 affected spontaneous motor activity in mice less than eperisone-HCl. The results of this study suggest that MS-322 is a potent centrally acting muscle relaxant with relatively weak depressant activity at other central nervous system pathways.
Otsu
T
T
Institute of Biological Science, Mitsui Pharmaceuticals Inc., Chiba, Japan.
Kawabata
H
H
Horikomi
K
K
Tanada
H
H
Sakai
K
K
Matsubara
A
A
Mizuchi
A
A
D000818:Animals; D002415:Cats; D003655:Decerebrate State / Q000503:physiopathology; D005260:Female; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009127:Muscle Rigidity / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000187:drug effects; D011427:Propiophenones / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology
D007555:Isoxazoles; D009125:Muscle Relaxants, Central; D011427:Propiophenones; D011759:Pyrrolidines; C107564:3-phenyl-5-(2-(1-pyrrolidinylmethyl)butyryl)isoxazole hydrochloride; C030848:eperisone