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N6-2-(4-aminophenyl)ethyl-adenosine enhances the anticonvulsive activity of antiepileptic drugs.

Abstract
N6-2-(4-Aminophenyl)ethyl-adenosine (APNEA, a non-selective agonist of the adenosine A3 receptors), at the subprotective dose of 1 mg/kg against electroconvulsions, significantly potentiated the anticonvulsive action of phenobarbital, diphenylhydantoin and valproate against maximal electroshock, being ineffective at lower doses. APNEA (0.0039-1 mg/kg) also enhanced the protective activity of carbamazepine. Aminophylline (5 mg/kg) and 8-cyclopentyl-1,3-dimethylxanthine (8-CPX, 5 mg/kg), reversed the APNEA (1 mg/kg)-induced enhancement of the anticonvulsive action of phenobarbital, diphenylhydantoin and valproate, but not that of carbamazepine produced by APNEA at 0.0039 mg/kg. The adenosine agonist did not alter the plasma levels of antiepileptic drugs studied, so a pharmacokinetic interaction is not probable. Finally, APNEA (0.0156 and 1 mg/kg) administered alone or in combination with carbamazepine significantly decreased the body temperature and impaired long-term memory. Our results suggest that APNEA at low doses potentiates the protective activity of carbamazepine most likely through the A subtype of adenosine receptors. At higher doses, APNEA seems to enhance the anticonvulsive effect of other antiepileptics via adenosine A1 receptors.
AuthorsK K Borowicz, Z Kleinrok, S J Czuczwar
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 327 Issue 2-3 Pg. 125-33 (May 30 1997) ISSN: 0014-2999 [Print] Netherlands
PMID9200550 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticonvulsants
  • N(6)-2-(4-aminophenyl)ethyladenosine
  • Purinergic P1 Receptor Agonists
  • Carbamazepine
  • Valproic Acid
  • Phenytoin
  • Adenosine
  • Phenobarbital
Topics
  • Adenosine (analogs & derivatives, pharmacology)
  • Animals
  • Anticonvulsants (pharmacology)
  • Body Temperature (drug effects)
  • Carbamazepine (pharmacology)
  • Darkness
  • Drug Synergism
  • Electroshock
  • Female
  • Memory (drug effects)
  • Mice
  • Motor Activity (drug effects)
  • Phenobarbital (pharmacology)
  • Phenytoin (pharmacology)
  • Purinergic P1 Receptor Agonists
  • Valproic Acid (pharmacology)

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