The behavioral effects of the calcium agonist Bay K 8644 in the mouse: antagonism by the calcium antagonist nifedipine.
Mice injected with the calcium agonist BAY K 8644 (2-4 mg/kg, i.p.) displayed profound behavioral changes including ataxia, decreased motor activity, Straub tail, arched back, limb clonus and tonus, and an increased sensitivity to auditory stimulation. BAY K 8644 significantly impaired rotorod performance in mice with an ED50 of 0.8 mg/kg. The behavioral effects of BAY K 8644 were antagonized by nifedipine, but not by the non-dihydropyridine calcium channel antagonist verapamil or the alpha-adrenoceptor antagonist prazosin. Further, the actions of BAY K 8644 were not mimicked by the alpha-adrenoceptor agonist methoxamine at doses up to 4.5 mg/kg. These observations, coupled with the findings that BAY K 8644 is a potent, competitive inhibitor of [3H]nitrendipine binding to the dihydropyridine binding site in mouse brain (Ki = 7.0 X 10(-9) M), suggests that BAY K 8644 may produce its behavioral actions via an interaction with the DHP binding site, which has been linked to the control of calcium flux across membranes in peripheral tissues.
Bolger
G T
GT
Weissman
B A
BA
Skolnick
P
P
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D009568:Nitrendipine
D002121:Calcium Channel Blockers; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009568:Nitrendipine; D009543:Nifedipine