Anticonvulsant action of 2-chloroadenosine against pentetrazol-induced seizures in immature rats is due to activation of A1 adenosine receptors.
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Abstracto
Potentiation of adenosinergic inhibitory modulation is one of possible strategies to develop new antiepileptic drugs. Nonspecific receptor agonist 2-chloroadenosine was tested against pentetrazol-induced convulsions in immature (7, 12, 18 and 25 days old) and adult rats. Doses of 1-15 mg/kg i.p. suppressed tonic phase of generalized tonic-clonic seizures (GTCS) in the two youngest groups, whereas GTCS were abolished in older rats. Minimal clonic seizures in 18-day and older rats were suppressed by high doses of 2-chloroadenosine. The role of A1 and A2A adenosine receptors was studied in 12- and 25-day-old rats. Action of an agonist of A1 receptors CCPA is similar to that of 2-chloroadenosine. An agonist of A2A receptors CGS 21680 exhibits an anticonvulsant action only in the dose-inducing catalepsy; an A2A antagonist ZM 241385 moderately suppressed tonic phase of GTCS only in 12-day-old animals. Anticonvulsant action of adenosine agonists is due to their effects on A1 receptors.