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

Abstract

1 The severity of anaemic decerebrate rigidity was quantitatively determined by measuring the frequency of electromyographic potentials in the rat. 2 Some oxazolidinones markedly reduced the severity ofthis decerebrate rigidity in a dose-dependent manner,one (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. 3 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. 4 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. 5 MLV-6976 reduced the severity of harmaline-induced tremor in mice in a dose-dependent manner, but slightly augmented tremorine-induced tremor. 6 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. 7 The amplitude of miniature endplate potentials of the rat diaphragm was decreased by MLV-6976 only at concentrations greater than 0.1 mM. 8 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.

Asymmetric Transfer Hydrogenation of α-Substituted-β-Keto Carbonitriles via Dynamic Kinetic Resolution

“…The target product 4d was obtained in high yield with undiminished enantioselectivity (>99% ee) after platinum-catalyzed hydration and simultaneous Hoffman degradation and ring-closing cascade . Notably, the chiral compound 4d can be transformed into Ipenoxazone in just one step according to the reported procedure (Scheme a) . The DKR-ATH reaction of 1o was also conducted on a gram scale, and 2o was obtained with 98% yield, 99% ee, and 95:5 dr.…”

“…62 Notably, the chiral compound 4d can be transformed into Ipenoxazone in just one step according to the reported procedure (Scheme 2a). 63 The DKR-ATH reaction of 1o was also conducted on a gram scale, and 2o was obtained with 98% yield, 99% ee, and 95:5 dr. The dr value could be increased to 99:1 after a simple recrystallization.…”

Current Updates on Oxazolidinone and Its Significance

“…(8) Centrally Acting Muscle Relaxants [ 80 ]. The severity of anaemic decerebrate rigidity was quantitatively determined by measuring the frequency of electromyographic potentials in the rat.…”

Coma and seizure caused by an afloqualone overdose

“…Afloqualone, an analogue of methaqualone developed in the 1980s in Japan, is a centrally acting muscle relaxant that affects the spinal polysynaptic reflexes and is used by patients with cervico‐omobrachial syndrome, lumbar pain, and spastic paralysis. An important side‐effect of the drug is photosensitization, causing skin symptoms such as dermatitis .…”