title: Some pharmacological studies on the spastic mouse.
abstract: 1 Full-wave rectification and integration of the EMG signal recorded from the hamstring muscles of the spastic mouse was used to evaluate the actions of a variety of drugs on the muscle rigidity of these mutants, animals in which no histological lesion has yet been found. 2 Profound and long-lasting muscle relaxant responses were consistently observed upon the injection of diazepam (2 mg/kg, i.p.) and flunitrazepam (2 mg/kg, i.p.). Such responses were always greater than those obtained upon injection of 40% (v/v) propylene glycol (10 ml/kg) alone, the vehicle for the benzodiazepines. 3 The muscle relaxant action of a low dose (0.25 mg/kg i.p.) of the benzodiazepine Roll-6896 was not shared by the same dose of its enantiomer Roll-6893. 4 Profound and long-lasting muscle relaxation was caused by sodium valproate (696 mg/kg, i.p.). Consistent muscle relaxant responses were also observed upon the injection of pentobarbitone (30 mg/kg, i.p.), but not phenobarbitone (30 mg/kg, i.p.). 5 Other drugs that had little or no detectable effect on the muscle rigidity of the spastic mouse included diphenylhydantoin (30 mg/kg, i.p.) and bromocriptine (10 mg/kg, s.c.) while, in some animals, benztropine (2 mg/kg, i.p.) and baclofen (10 mg/kg, i.p.) increased muscle rigidity. 6 The development of full muscle relaxant responses to flunitrazepam (2 mg/kg, i.p.) and to sodium valproate (696 mg/kg, i.p.) was shown to depend upon mild warming of the animals with radiant heat, a procedure which can increase muscle spindle afferent input to the spinal cord. 7 The results suggest a hyperactivity of stretch reflexes in the spastic mouse, ameliorated selectively by those drugs that enhance the GABA-mediated presynaptic inhibition of such pathways.
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D004576:Electromyography; D005260:Female; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009128:Muscle Spasticity / Q000503:physiopathology*; D009132:Muscles / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D000927:Anticonvulsants; D009125:Muscle Relaxants, Central; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid