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.
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.
D000818:Animals; D001569:Benzodiazepines / Q000037:antagonists & inhibitors*; D001570:Benzodiazepinones / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004336:Drug Antagonism; D005442:Flumazenil; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D001570:Benzodiazepinones; D001569:Benzodiazepines; D005442:Flumazenil; D009020:Morphine; D003975:Diazepam