Muscle relaxant action of 2-chloroadenosine in genetically spastic rats is independent of gamma-aminobutyric acid-mediated inhibition.
The role played by benzodiazepine (BDZ) receptors and GABAergic mechanisms in the muscle relaxant effect of the adenosine receptor agonist, 2-chloroadenosine (2-CLA) was evaluated in genetically spastic rats. 2-CLA reduced in a dose-related manner the spontaneous tonic activity in the electromyogram (EMG) of the gastrocnemius-soleus muscle. While the muscle relaxant effect produced by the adenosine analogue was abolished by aminophylline, a methylxanthine with potent antagonistic activity of adenosine-mediated inhibition, the two gamma-aminobutyric acid (GABA) antagonists bicuculline and picrotoxin did not reverse it. Neither Ro 15-1788 nor CGS 8216, specific BDZ receptor antagonists, nor beta-carboline-3-carboxylic acid methyl ester, an inverse agonist at BDZ receptors, affected the depressant effect of 2-CLA in the EMG. These results suggest that 2-CLA does not interact with GABA or BDZ receptor-mediated events in vivo to produce the muscle relaxant action. It is proposed that purinergic mechanisms may be involved in the muscle relaxant effects of a variety of drugs.
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D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004347:Drug Interactions; D005260:Female; D008297:Male; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009128:Muscle Spasticity / Q000188:drug therapy* / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*
D009125:Muscle Relaxants, Central; D011963:Receptors, GABA-A; D015762:2-Chloroadenosine; D000241:Adenosine