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.