The pharmacological properties of CS-722, a newly synthesized centrally acting muscle relaxant.
The pharmacological properties of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized, centrally acting muscle relaxant, were studied in rats. The drug CS-722 reduced the radio frequency decerebrate rigidity in a dose-dependent manner (25-100 mg/kg, p.o.); it inhibited the increase in discharges from Ia afferent fibers, gamma-motor activity, which was induced by stimulation of the reticular formation. The compound, however, showed no effect on the basal discharge of Ia afferent fibers. The polysynaptic reflex was depressed by CS-722, with less influence on the monosynaptic reflex in intact and spinal preparations and CS-722 did not prolong thiopental-induced sleeping time. In rats anesthetized with halothane, CS-722 did not affect the electroencephalogram (EEG) arousal response, which was elicited by stimulation of the reticular formation. The results of this study suggest that CS-722 can exert a muscle relaxant action, at a dose range at which depression of the ascending reticular activating system was negligible. The results also suggest that depressions of the gamma-motor system and the polysynaptic reflex may contribute to the muscle relaxant action of CS-722.
Tanabe
M
M
New Lead Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.
Kaneko
T
T
Tonohiro
T
T
Iwata
N
N
D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003655:Decerebrate State / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009047:Motor Neurons, Gamma / Q000187:drug effects; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009127:Muscle Rigidity / Q000517:prevention & control; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013874:Thiopental / Q000494:pharmacology
D007555:Isoxazoles; D009025:Morpholines; D009125:Muscle Relaxants, Central; D010276:Parasympatholytics; C077576:CS 722; C023754:tizanidine; D013874:Thiopental; D003000:Clonidine