title: Pharmacological properties of NK433, a new centrally acting muscle relaxant.
abstract: The pharmacological properties of NK433 ((-)-(R)-2-methyl-3-(1-pyrrolidinyl)-4'-trifluoromethylpropiophenone+ ++ monohydrochloride), a novel muscle relaxant, were investigated. NK433 inhibited intercollicular decerebrate rigidity (gamma-rigidity) and anemic decerebrate rigidity (alpha-rigidity) dose dependently. NK433 was stronger in inhibiting gamma-rigidity than alpha-rigidity. NK433 inhibited the increase in muscle spindle discharges induced by pinna pinching (gamma-activity) without affecting muscle spindle discharges or neuromuscular transmission. At muscle relaxant doses in decerebrate rigidities, NK433 did not affect the muscle tone induced by morphine-HCl nor that of normal animals. These results suggest that NK433 selectively depresses the excessive muscle tone of decerebrate rigidities through its effects on the central nervous system, and inhibition of gamma-activity causes a preferential depression of gamma-rigidity in comparison to alpha-rigidity. In i.v. experiments, the effects of NK433 on decerebrate rigidities were similar to those of eperisone-HCl and tolperisone-HCl, but in p.o. experiments, NK433 was at least 3 times as potent as eperisone-HCl and tolperisone-HCl.
authors.affiliation: Research Laboratories, Pharmaceuticals Group, Nippon Kayaku Co. Ltd., Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sakitama
authors.forename: Y
authors.initials: Y
authors.lastname: Ozawa
authors.forename: N
authors.initials: N
authors.lastname: Aoto
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009121:Muscle Denervation; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009127:Muscle Rigidity / Q000188:drug therapy; D009470:Muscle Spindles / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D011427:Propiophenones / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects; D014049:Tolperisone / Q000494:pharmacology
chemical_list: D000700:Analgesics; D009125:Muscle Relaxants, Central; D011427:Propiophenones; D011759:Pyrrolidines; C030848:eperisone; D009020:Morphine; D014049:Tolperisone; C093390:NK 433