Effects of concurrent subchronic treatments with desmethylimipramine and propranolol on beta-adrenergic and serotonin₂ receptors in rat brain

Abstract

The effects of seven consecutive daily injections of desmethylimipramine (DMI 20 mg/kg) and propranolol (PRO 10 mg/kg) on³H-dihydroalprenolol (³H-DHA) and³H-ketanserin (³H-KET) binding in rat brain were examined. Analyses of saturation binding data using the iterative, nonlinear curve-fitting program LIGAND revealed that PRO increased, while DMI reduced,³H-DHA binding site density in cerebral cortex without altering receptor affinity, as previously reported. DMI reduced³H-KET binding site density without changing affinity, and PRO produced the same effect. In cerebral cortex and probably in hippocampus and striatum, DMI and PRO administered together increased the density of³H-DHA binding sites (beta-adrenergic receptors) and reduced their affinity. This combination of drugs reduced the density of³H-KET binding sites (5-HT₂ receptors) in cerebral cortex, but did not change their affinity. These findings indicate a need for additional studies on the interactions of DMI and PRO and related drugs because of implications for the treatment of depressed patients with cardiovascular disorders.