Reversal of the muscle relaxant effect of diazepam by the specific benzodiazepine antagonist Ro 15-1788: an electromyographic study in morphine model of muscular rigidity in rats.

Abstract

The effects of the benzodiazepines diazepam and midazolam on the rigidity produced by systemic administration of morphine (15 mg/kg i.p.) were studied in rats. The rigidity was recorded as a tonic activity from the gastrocnemius-soleus muscle of non-anesthetized rats in the electromyogram. Both diazepam (1-5 mg/kg i.p.) and midazolam (2.5 and 5 mg/kg i.p.), when administered 45 min after morphine, temporarily antagonized the muscular rigidity. When the competitive antagonist Ro 15-1788 (ethyl-8-fluoro-5, 6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5a]-[1,4]benzodiazepine-3 -carboxylate) (5 mg/kg i.p.) was administered together with diazepam (5 mg/kg i.p.), it prevented the effect of diazepam, although by itself it did not affect the morphine-induced muscular rigidity. Our results suggest that diazepam, by acting on benzodiazepine receptors, can antagonize the morphine-induced muscular rigidity. The latter phenomenon might serve as a model for some types of muscular rigidity observed in humans.

• Authors: L Turski, U Havemann, K Kuschinsky
• Journal: Life sciences (Life Sci) Vol. 33 Suppl 1 Pg. 755-8 ( 1983) ISSN: 0024-3205 [Print] Netherlands
• PMID: 6420630 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzodiazepinones
• Benzodiazepines
• Flumazenil
• Morphine
• Diazepam

Topics

• Animals
• Benzodiazepines (antagonists & inhibitors)
• Benzodiazepinones (pharmacology)
• Diazepam (pharmacology)
• Drug Antagonism
• Flumazenil
• Male
• Morphine (pharmacology)
• Muscle Contraction (drug effects)
• Muscle Relaxation (drug effects)
• Rats
• Rats, Inbred Strains