BINDING OF H3-IMIPRAMINE, H3-DIMETACRINE AND S35-CHLORPROMAZINE TO SYNAPTOSOMES

Abstract

Binding of 3H-imipramine, 3H-dimetacrine and 35S-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.degree. C, representing a typical binding mode with 2 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 3H-dimetacrine and 35S-chlorpromazine represented a single binding mode whereas 3H-imipramine showed a multiple one. When the synaptosomes were treated by freezing and thawing 15 times, a high affinity binding component of 3H-imipramine was not observed, while the other 2 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 3H-imipramine were carried out using myelin fragments of rat cerebral cortex. In the myelin fragments preparation, 2 typical classes of binding mode as shown in the synaptosomes were also recognized. A double reciprocal plot of the saturable binding component showed only a straight line, i.e., single binding mode. Imipramine has multiple binding sites to synaptosomes and a high affinity binding component is affected by freezing and thawing procedure.