Disease relevance of 4-chloro-2-[(2R)-2-hydroxy-3-morpholino-propyl]-5-phenyl-isoxazol-3-one

• The drug CS-722 reduced the radio frequency decerebrate rigidity in a dose-dependent manner (25-100 mg/kg, p.o.); it inhibited the increase in discharges from Ia afferent fibers, gamma-motor activity, which was induced by stimulation of the reticular formation [1].
• 1. The pharmacological properties of the centrally acting muscle relaxant, CS-722, were studied in cultured hippocampal cells and dorsal root ganglion cells of the rat using the whole-cell variation of the patch clamp technique [2].

High impact information on 4-chloro-2-[(2R)-2-hydroxy-3-morpholino-propyl]-5-phenyl-isoxazol-3-one

• 3. CS-722 reduced voltage-gated sodium currents, while shifting the sodium channel inactivation curve to more negative membrane potentials [2].
• The polysynaptic reflex was depressed by CS-722, with less influence on the monosynaptic reflex in intact and spinal preparations and CS-722 did not prolong thiopental-induced sleeping time [1].
• Preferential enhancement of inhibitory synaptic transmission by CS-722 in the ventral horn neurons of neonatal rat spinal cord [3].
• Moreover, CS-722 reduced paired pulse facilitation of gamma-aminobutyric acid (GABA)-mediated IPSCs, suggesting its action on the presynaptic terminal [3].
• When administered i.c.v. (50 and 100 micrograms) or i.t. (200 and 400 micrograms), CS-722 reduced the radio frequency decerebrate rigidity, although the effect after i.c.v. injection was transient [4].

Biological context of 4-chloro-2-[(2R)-2-hydroxy-3-morpholino-propyl]-5-phenyl-isoxazol-3-one

• The drug CS-722 (50 mg/kg, i.v.) depressed the polysynaptic reflex but was less effective on the monosynaptic reflex [5].
• Spinal reflexes were not affected by CS-722 injected i.c.v. It seems that muscle relaxation is not always accompanied by impairment of the spinal reflex [4].

Anatomical context of 4-chloro-2-[(2R)-2-hydroxy-3-morpholino-propyl]-5-phenyl-isoxazol-3-one

• Doses injected intra-4th ventricularly (i.c.v.) or intrathecally (i.t.) were determined according to measurements of CS-722 concentration in the brain stem and the spinal cord after systemic administration [4].

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