Pharmacological properties of NK433, a new centrally acting muscle relaxant

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 (γ-rigidity) and anemic decerebrate rigidity (α-rigidity) dose dependently. NK433 was stronger in inhibiting γ-rigidity than α-rigidity. NK433 inhibited the increase in muscle spindle discharges induced by pinna pinching (γ-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 γ-activity causes a preferential depression of γ-rigidity in comparison to α-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.