Selective protection by adenosine receptor agonists against DMCM-induced seizures.
The anticonvulsant actions of the adenosine receptor agonists, 1-phenylisopropyladenosine, 2-chloroadenosine and cyclohexyl-adenosine, against DMCM (methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate)-induced seizures in mice were studied with an infusion technique. 2-Chloroadenosine and cyclohexyladenosine were active at 1 mg/kg whereas 1-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 1-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.
Petersen
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Department of Pharmacology, Dumex A/S, Copenhagen S, Denmark.
D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline; D002243:Carbolines / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003292:Convulsants / Q000494:pharmacology*; D005260:Female; D051379:Mice; D010433:Pentylenetetrazole; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013806:Theophylline / Q000494:pharmacology
D000927:Anticonvulsants; D002243:Carbolines; D003292:Convulsants; D011983:Receptors, Purinergic; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D015762:2-Chloroadenosine; D010660:Phenylisopropyladenosine; C027513:N(6)-cyclohexyladenosine; C038933:ZK 91296; D013806:Theophylline; D000241:Adenosine; D010433:Pentylenetetrazole; D001640:Bicuculline