Binding of H3-imipramine, H3-dimetacrine and S35-chlorpromazine to synaptosomes.

Binding of H3-imipramine, H3-dimetacrine and S35-chlorpromazine to synaptosomes of rat cerebral cortex was studied using a centrifugation method, and kinetic analysis of the experimental data. Three psychotropic drugs were shown to be rapidly bound to synaptosomes at 2 degrees C, representing a typical binding mode with two classes of binding components, i.e., saturable and non-saturable binding. A double reciprocal plot of the saturable binding component of these drugs revealed that H3-dimetacrine and S35-chlorpromazine represented a single binding mode, whereas H3-imipramine showed a multiple one. When the synaptosomes were treated by freezing and thawing 15 times, a high affinity binding component of H3-imipramine was not observed, while the other two drugs showed a single binding mode as well as those of the undisrupted synaptosomes. To investigate the specificity of this multiple binding mode, comparative binding studies of H3-imipramine were carried out using myelin fragments of rat cerebral cortex. In the myelin fragments preparation, two typical classes of binding mode as shown in the synaptosomes were also recognized. However, a double reciprocal plot of the saturable binding component showed only a straight line, i.e., single binding mode. These findings suggest that imipramine has multiple binding sites to synaptosomes and a high affinity binding component is affected by freezing and thawing procedure.