Selective protection by adenosine receptor agonists against DMCM-induced seizures

Abstract

The anticonvulsant actions of the adenosine receptor agonists, 1-phenylisopropyladenosine, 2-chloroadenosine and cyclohexyladenosine, against DMCM (methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate)-induced seizures in mice were studied with an infusion technique. 2-Chloroadenosine and cyclohexyladenosine were active at 1 mg/kg whereas l-phenyl-isopropyladenosine was active at 0.03 mg/kg given i.p. At 10 mg/kg, 1-phenylisopropyladenosine was only weakly active against pentylenetetrazol-induced seizures and not active against bicuculline-induced seizures. The selective effect of l-phenylisopropyladenosine against DMCM-induced seizures suggests that adenosine receptor agonists may allosterically counteract the negative modulating effect of DMCM on GABA coupling to the chloride channel. This indicates that adenosine receptors may have a physiological function within the GABA/benzodiazepine receptor complex in the brain.