Inhibition of 3H-imipramine binding by plasma from depressed and normal subjects

The inhibition by human plasma of 3H-imipramine (3H-IMI) specific binding to rat cerebral membranes was investigated using platelet-free plasma (PFP) from normal and depressed subjects. The specific binding of 3H-IMI at a ligand concentration of 4 nM decreased with increasing PFP volumes, reaching 50% inhibition following the addition of 10-13 microliters PFP to a final incubation volume of 250 microliters. The extent of this inhibition was the same using PFP from controls or depressed patients. The inhibitory activity was associated with plasma proteins. Scatchard analysis of 3H-IMI binding in the presence and absence of PFP indicated that the inhibitory effect was associated with an increased Kd without an appreciable change in Bmax. It is suggested that an endogenous acceptor in the PFP, such as alpha 1-acid-glycoprotein may be responsible for the observed inhibition of 3H-IMI binding to the cerebral membranes.