Anticonvulsant action of 2-chloroadenosine against pentetrazol-induced seizures in immature rats is due to activation of A1 adenosine receptors

J Neural Transm (Vienna). 2010 Nov;117(11):1269-77. doi: 10.1007/s00702-010-0465-9. Epub 2010 Aug 31.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Chloroadenosine / pharmacology*
  • Animals
  • Anticonvulsants / pharmacology*
  • Convulsants / toxicity
  • Male
  • Pentylenetetrazole / toxicity
  • Rats
  • Rats, Wistar
  • Receptor, Adenosine A1 / drug effects*
  • Receptor, Adenosine A1 / metabolism*
  • Seizures / chemically induced
  • Seizures / metabolism*

Substances

  • Anticonvulsants
  • Convulsants
  • Receptor, Adenosine A1
  • 2-Chloroadenosine
  • Pentylenetetrazole