Binding of beta-carbolines and tetrahydroisoquinolines by opiate receptors of the delta-type

Abstract

Effects of various beta-carbolines (BC's) and two tetrahydroisoquinolines (TIQ's) on the specific binding of a natural opiate delta-receptor ligand, leucine enkephalin, have been studied in rat synaptosomal membranes, and compared with the effects on the binding of mu-receptor ligands dihydromorphine and naloxone. Harmaline (7-MeO-1-Me-dihydro-BC) was the most potent compound studied (Ki value 3.5 microM), while the two TIQ's (salsolinol and salsolidine) were less potent than BC's (Ki greater than 100 microM) in inhibiting the binding of delta-receptors. In general, BC's showed more affinity for delta-receptors than for mu-receptors; salsolinol was more potent against the binding of mu-receptors. Inhibition of binding was generally of the competitive type: Kd values increased and Bmax values were not altered. The Na dependence suggests that BC's and salsolinol are antagonists or partial agonists of opioids. Since the binding affinity of BC's and TIQ's was on the micromolar level only, the opiate receptors do not appear to be the major sites of action for BC's or TIQ's.