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PubMed1985

Electrophysiological analysis of the mode of action of muscle relaxants in spasticity.

Variations in four electrophysiological tests (H/M, T/M, vibratory inhibition, and recovery curve of Hoffmann's reflex following stimulation at the ankle) were studied following a single administration of four myorelaxant drugs: diazepam (10 mg intramuscularly), baclofen (20 mg intramuscularly), tizanidine (4 mg orally), and idrocilamide (60 mg intramuscularly). Fifty-one spastic patients, divided into four groups, were tested. All four drugs reduced the H/M and T/M ratios very slightly. Only diazepam and tizanidine reinforced vibratory inhibition. Diazepam and tizanidine did not modify the abnormal recovery curves, however, whereas baclofen and idrocilamide did. Reinforcement of vibratory inhibition suggests an increase in presynaptic inhibition mediated by gamma-aminobutyric acid; changes in recovery curves are likely due to modifications of interneuronal reactivity. Matching myorelaxants to the predominant pathophysiological abnormality detected by electrophysiological exploration may lead to better treatment of spasticity.

Baclofen↗
PubMed1997

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.

Administration, Oral↗
PubMed1986

A new class of potent centrally acting muscle relaxants: pharmacology of oxazolidinones in rat decerebrate rigidity.

The severity of anaemic decerebrate rigidity was quantitatively determined by measuring the frequency of electromyographic potentials in the rat. Some oxazolidinones markedly reduced the severity of this decerebrate rigidity in a dose-dependent manner, (4S,5R)-4-(2-methylpropyl)-3- [3-(perhydroazepin-1-yl)propyl]-5-phenyl-1,3-oxazolidin-2-on e (MLV-6976) being the most potent. In addition to the oxazolidinones, an aminoalcohol derivative, (1RS,2SR)-5-methyl-1-phenyl-2-(3-piperidinopropylamino )hexan-1-ol (MLV-5860) also reduced the rat decerebrate rigidity. In the oxazolidinone series, the optical isomers with absolute configuration (S) at the 4-position were more potent than the corresponding (4R)-isomers, while there was no significant difference in their LD50 values. Normal rats and mice receiving MLV-6976 at doses which reduced decerebrate rigidity showed no behavioural changes, impairment of motor coordination only appearing at extremely high doses. MLV-6976 and its derivatives did not affect spinal reflex potentials in cats. MLV-6976 reduced the severity of harmaline-induced tremor in mice in a dose-dependent manner, but slightly augmented tremorine-induced tremor. The frequency of the spike discharges induced by iontophoretically applied glutamate was reduced by MLV-6976 in a dose-dependent manner in rat cortical neurones. The amplitude of miniature endplate potentials of the rat diaphragm was decreased by MLV-6976 only at concentrations greater than 0.1 mM. It is concluded that MLV-6976 acts on the brainstem or/and higher levels of the brain rather than on the spinal cord or the peripheral nervous system to reduce the excessive activities of the nervous system.

Animals↗