Lack of major effects on mouse brain adenosine A1 receptors of oral carbamazepine and calcium antagonists.
Interaction with adenosine A1 receptors is a possible contributory mechanism to the anticonvulsant effects of carbamazepine (CBZ) and the dihydropyridine calcium antagonists. We measured the binding of [3H]cyclohexyladenosine to adenosine A1 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 (Kd) and receptor numbers (Bmax) were calculated using Scatchard and saturation isotherm analyses. Mean Kds (SEM) in control brain stem, cerebellum, and cortex were 2.09 (0.31), 2.39 (0.2), and 3.12 (0.28) nM, respectively. Results of Bmax for the same areas were 188 (26), 280 (24), and 449 (54) fmol/mg protein. Nifedipine (p less than 0.005) and NMD (p less than 0.02) raised the Kd of A1 receptors only in the cerebellum, and CBZ increased cerebellar Bmax (p less than 0.05). These minor effects on A1 receptors in CF1 mice, when given in doses previously shown to have anticonvulsant properties in these animals, do not suggest that alteration in A1 receptor activity is an important mechanism for the anticonvulsant effects of these drugs.
Larkin
J G
JG
University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland.
Thompson
G G
GG
Scobie
G
G
Drennan
J E
JE
Brodie
M J
MJ
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D002220:Carbamazepine / Q000378:metabolism / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009543:Nifedipine / Q000378:metabolism / Q000494:pharmacology; D009553:Nimodipine / Q000378:metabolism / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000187:drug effects*
D002121:Calcium Channel Blockers; D011983:Receptors, Purinergic; D002220:Carbamazepine; D009553:Nimodipine; D009543:Nifedipine; D000241:Adenosine