Effects of a new centrally acting muscle relaxant, NK433 (lanperisone hydrochloride) on spinal reflexes.
(-)-(R)-2-methyl-3-(1-pyrrolidinyl)-4'-trifluoromethylpropiophenone++ + monohydrochloride, lanperisone hydrochloride (NK433) administered intravenously or orally depressed the mono- and polysynaptic reflex potential, dorsal root reflex potential, flexor reflex mediated by group II afferent fibers, patellar and flexor reflexes. These effects were reduced by spinal transection. NK433 inhibited the facilitation of the flexor reflex mediated by group II afferent fibers that was induced by intrathecal administration of noradrenaline-HCl. (+)-(1R,2R)-2-methyl-3-(1-pyrrolidinyl)-1-(4-trifluoromethylphenyl)-1-pr opanol (LPS-9)-HCl, a metabolite of NK433, also inhibited the spinal reflexes. Given orally, NK433 had effects more than three times stronger and tending to be longer-lasting than those of eperisone-HCl. These results suggest that NK433 exerts a non-selective inhibition on spinal reflexes and that inhibition of the descending noradrenergic tonic facilitation within the spinal cord is involved in the mechanism of spinal reflex depression by NK433. LPS-9 could contribute to the potent activity of NK433 after oral administration.
Sakitama
K
K
Research and Development Division, Nippon Kayaku Co. Ltd., Tokyo, Japan.
Ozawa
Y
Y
Aoto
N
N
Tomita
H
H
Ishikawa
M
M
D000284:Administration, Oral; D000818:Animals; D000440:Butanols / Q000494:pharmacology; D002818:Cordotomy; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D017847:Patellar Ligament / Q000187:drug effects / Q000502:physiology; D011427:Propiophenones / Q000008:administration & dosage / Q000494:pharmacology*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D012026:Reflex, Stretch / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D014049:Tolperisone / Q000008:administration & dosage / Q000494:pharmacology
D000440:Butanols; C110575:LPS 9; D009125:Muscle Relaxants, Central; D011427:Propiophenones; D011759:Pyrrolidines; C030848:eperisone; D014049:Tolperisone; C093390:NK 433; D009638:Norepinephrine