Pharmacological characterization of [3H] desipramine binding in rat cerebral cortex

Abstract

• 1.

  1. The specific binding of [³H]desipramine to membranes from rat brain cortex is biphasic and the Scatchard analysis of data shows two distinct components: the high affinity component, with a dissociation constant (K_D) of 4.5 nM and the low affinity component (K_D = 80 nM).

• 2.

  2. Different order of potency in displacing the high affinity [³H]desipramine and [³H]imipramine binding was shown by various compounds tested. Nortriptyline and nisoxetine were the most potent displacers of [³H]desipramine specific binding while chlorimipramine and fluoxetine showed highest potency in competing for [³H]imipramine binding sites.

• 3.

  3. Significant correlation was found between the ability of various drugs to inhibit [³H]desipramine binding and their potency to block the neuronal uptake of noradrenaline in brain.

• 4.

  4. The results suggest that the high affinity binding of [³H]desipramine is distinct from that of [³H]imipramine and is most likely associated with sites involved in neuronal uptake of noradrenaline.