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.
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Authors | K K Borowicz, Z Kleinrok, S J Czuczwar |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 327
Issue 2-3
Pg. 125-33
(May 30 1997)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 9200550
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anticonvulsants
- N(6)-2-(4-aminophenyl)ethyladenosine
- Purinergic P1 Receptor Agonists
- Carbamazepine
- Valproic Acid
- Phenytoin
- Adenosine
- Phenobarbital
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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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