title: 2-Chloroadenosine, a preferential agonist of adenosine A1 receptors, enhances the anticonvulsant activity of carbamazepine and clonazepam in mice.
abstract: 2-Chloroadenosine (0.25-1 mg/kg) significantly raised the threshold for electroconvulsions in mice. This preferential adenosine A(1) receptor agonist (at 0.125 mg/kg) significantly potentiated the protective activity of carbamazepine against maximal electroshock-induced seizures in mice. 2-Chloroadenosine (1 mg/kg) showed also anticonvulsive efficacy against pentylenetetrazol-evoked seizures, raising the CD(50) value for pentylenetetrazol from 77.2 to 93.7 mg/kg. The drug (at 0.5 mg/kg) significantly enhanced the protective action of clonazepam in this test, decreasing its ED(50) value from 0.033 to 0.011 mg/kg. Moreover, aminophylline, a non-selective adenosine receptor antagonist (5 mg/kg), and 8-cyclopentyl-1,3-dimethylxanthine (8-CPX), a selective A(1) adenosine receptor antagonist (5 mg/kg) reversed the 2-chloroadenosine (0.125 mg/kg)-induced enhancement of the protective activity of carbamazepine and clonazepam. 2-Chloroadenosine administered alone or combined with antiepileptic drugs, caused neither motor nor long-term memory impairment. Finally, the adenosine A(1) agonist did not change the free plasma concentration of antiepileptics, so a pharmacokinetic factor is not probable. Summing up, 2-chloroadenosine potentiated the protective activity of both carbamazepine and clonazepam, which seems to be associated with the enhancement of purinergic transmission mediated through adenosine A(1) receptors.
authors.affiliation: Department of Pathophysiology, Lublin Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
authors.forename: Kinga K
authors.initials: KK
authors.lastname: Borowicz
authors.forename: Jarogniew
authors.initials: J
authors.lastname: Łuszczki
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Czuczwar
mesh_terms: D015762:2-Chloroadenosine / Q000627:therapeutic use*; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use*; D002220:Carbamazepine / Q000097:blood / Q000627:therapeutic use*; D002998:Clonazepam / Q000097:blood / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004597:Electroshock / Q000706:statistics & numerical data; D008297:Male; D051379:Mice; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1 / Q000502:physiology; D012640:Seizures / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D015762:2-Chloroadenosine; D002220:Carbamazepine; D002998:Clonazepam