AbstractCatecholamine‐derived alkaloids of the simple tetrahydroisoquinoline, 1‐benzyltetrahydroisoquinoline and tetrahydroprotoberberine classes have been tested for their ability to inhibit the binding of seven different radioligands to neurotransmitter receptors of brain synaptic membranes. Alkaloids of all three classes were active in inhibiting3H‐clonidine binding to α2‐adrenergic receptors. Stereoselectivity of tetrahydropapaveroline in binding to α2‐adrenergic receptors was evidenced by the marked activity of the S‐(—) isomer (IC50= 0.65 m̈M) in comparison to the R‐(+) enantiomer (IC50= 50 m̈M). The simple tetrahydroisoquinolines (3,4‐dihydroxytetrahydroisoquinoline and salsolinol), the four isomeric mono‐0‐methyl derivatives of 2,3,10,11‐tetrahydroxyberbine and tetrahydropapaveroline were the most potent inhibitors of30H‐apomorphine binding to dopaminergic receptor agonist sites. The tetrahydroprotoberberines, as a class, were the most potent inhibitors of3H‐spiroperidol binding to dopaminergic receptor antagonist sites and of3H‐WB‐4101 binding to α1‐adrenergic receptors. The 1‐benzyltetrahydroisoquinolines exhibited varying degrees of interaction with β1‐adrenergic receptors. Tetrahydropapaveroline (IC50= 0.3 m̈M) was the most active of the 24 alkaloids tested in inhibiting binding of3H‐dihydroalprenolol to β1‐adrenergic receptors. None of the alkaloids significantly affected3H‐QNB binding to muscarinic‐cholinergic receptors, and selected alkaloids from each class i