Stereoselective High‐Affinity Binding of3H‐Alaproclate to Membranes from Rat Cerebral Cortex

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Abstract
The binding of3H‐alaproclate, a selective 5‐hydroxytryptamine uptake inhibitor, to membranes prepared from the rat cerebral cortex was investigated by a filtration technique. It was found that3H‐alaproclate bound with high affinity to three or four different sites and to one low affinity site. The binding to two of these sites was displaceable by 1 μM proadifen (SKF 525A), an inhibitor of drug metabolism. From iterative nonlinear regression analysis the KD‐values of these sites were calculated to about 1 and 28 nM and the Bmaxvalues 1.5 and 19 pmol/g wet tissue, respectively. The high affinity binding that was not displaceable by proadifen but by 10 μM alaproclate had KD‐values of 1 nM and 6 nM and Bmax‐values of 0.4 and 2 pmol/g wet tissue. The low affinity binding that was not displaceable by proadifen had a KD‐value of about 200 nM and a Bmax‐value of about 90 pmol/g tissue. The possible relationship between the proadifen sensitive high affinity binding of3H‐alaproclate and the brain cytochrome P‐450 is discussed.