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.