Calcium channel antagonist binding sites labeled by 3H-nimodipine in human brain.

In vitro binding of 3H-nimodipine to human brain membranes is demonstrated in this study. This binding was specific and saturable, and had an apparent affinity constant (KD) of 0.27 nM. The maximal number of binding sites for 3H-nimodipine was 5.8 pmoles/gm wet weight of human frontal cortex. The binding was shown to be dependent on calcium, with half-maximal stimulation obtained at 3 X 10(-5) M CaCl2. Other 1,4-dihyropyridine calcium antagonists were shown to be competitive antagonists of 3H-nimodipine binding. In contrast, the calcium antagonists, verapamil and diltiazem, had complex interactions with 3H-nimodipine binding. These results represent the first identification of 3H-calcium antagonist binding sites in human brain, and they confirm that various calcium antagonist drugs may differ with respect to both their potency and their molecular site of action.