Seizure suppression by adenosine A(2A) receptor activation in a rat model of audiogenic brainstem epilepsy.
Adenosine is known to suppress seizure activity mainly by activation of adenosine A(1) receptors. However, little is known about the potential involvement of other types of adenosine receptors in seizure suppression. It was now tested whether activation of adenosine A(2A) receptors would be effective in the suppression of generalized brainstem seizures. Genetically epilepsy-prone rats were intraperitoneally injected with increasing doses of the A(2A) receptor agonist, 5'-(N-cyclopropyl)-carboxamido-adenosine (CPCA), and, for comparison, with the A(1) receptor agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA). Both CPCA and CCPA were effective in suppressing generalized brainstem seizures with minimal effective concentrations of 2.5 and 1.5 mg/kg, respectively. Seizure suppression was maintained when CPCA was co-injected with the peripherally acting adenosine receptor antagonist 8-(p-sulphophenyl)theophylline, suggesting that central activation of A(2A) receptors effectively contributes to seizure suppression.
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Alexander
A
Huber
Martin
M
Güttinger
Hanns
H
Möhler
Detlev
D
Boison
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001933:Brain Stem / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020195:Epilepsy, Reflex / Q000188:drug therapy*; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D011922:Rats, Mutant Strains; D043705:Receptor, Adenosine A2A
D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; C058394:2-chloro-N(6)cyclopentyladenosine; C024311:N-cyclopropyl adenosine-5'-carboxamide; D000241:Adenosine