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Lack of Major Effects on Mouse Brain Adenosine A 1 Receptors of Oral Carbamazepine and Calcium Antagonists
Author(s) -
Larkin John G.,
Thompson George G.,
Scobie Gordon,
Drennan Joan E.,
Brodie Martin J.
Publication year - 1991
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1991.tb04717.x
Subject(s) - anticonvulsant , chemistry , cerebellum , medicine , endocrinology , carbamazepine , receptor , nifedipine , pharmacology , adenosine , nimodipine , adenosine receptor , calcium , epilepsy , agonist , biology , biochemistry , neuroscience
Summary: Interaction with adenosine A 1 receptors is a possible contributory mechanism to the anticonvulsant effects of carbamazepine (CBZ) and the dihydropyridine calcium antagonists. We measured the binding of [ 3 H]cyclohexyladenosine to adenosine A 1 receptors in mouse brain stem, cerebellum, and cortex after oral administration of nifedipine, nimodipine (NMD), and CBZ for 7 days and compared the results with binding in control mice. Equilibrium dissociation constant (K d ) and receptor numbers (B max ) were calculated using Scatchard and saturation isotherm analyses. Mean K d s (SEM) in control brain stem, cerebellum, and cortex were 2.09 (0.31), 2.39 (0.2), and 3.12 (0.28) n M , respectively. Results of B max for the same areas were 188 (26), 280 (24), and 449 (54) fmol/mg protein. Nifedipine (p < 0.005) and NMD (p < 0.02) raised the K d of A 1 receptors only in the cerebellum, and CBZ increased cerebellar B max (p < 0.05). These minor effects on A, receptors in CF1 mice, when given in doses previously shown to have anticonvulsant properties in these animals, do not suggest that alteration in A 1 receptor activity is an important mechanism for the anticonvulsant effects of these drugs.