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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.
AuthorsT J Biscoe, J P Fry
JournalBritish journal of pharmacology (Br J Pharmacol) Vol. 75 Issue 1 Pg. 23-35 (Jan 1982) ISSN: 0007-1188 [Print] England
PMID7074284 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticonvulsants
  • Muscle Relaxants, Central
  • Benzodiazepines
  • gamma-Aminobutyric Acid
Topics
  • Animals
  • Anticonvulsants (pharmacology)
  • Benzodiazepines (pharmacology)
  • Electromyography
  • Female
  • Male
  • Mice
  • Mice, Mutant Strains
  • Muscle Relaxants, Central (pharmacology)
  • Muscle Relaxation (drug effects)
  • Muscle Spasticity (physiopathology)
  • Muscles (drug effects)
  • gamma-Aminobutyric Acid (physiology)

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