Pharmacology: α‐Adrenoceptor Interaction of Tetrandrine and Isotetrandrine in the Rat: Functional and Binding Assays

The action of 1 S ,1′ S ‐tetrandrine, a bisbenzyltetrahydroisoquinoline alkaloid, on α 1 ‐adrenoceptors has been compared with that of its isomer 1 R ,1′ S ‐isotetrandrine. The work includes binding assays to analyse the affinity of these products for the [ 3 H]prazosin binding site of rat cerebral cortical membranes and functional studies on rat isolated aorta to examine the effects of both alkaloids on intracellular calcium processes related or not to α‐adrenoceptor activation. A radioligand receptor‐binding study showed that both compounds interacted with the α 1 ‐adrenoceptors displacing [ 3 H]prazosin from the specific binding site. The K i values (inhibition constants) were 0.69±0.12 and 1.6±0.4 μM for tetrandrine and isotetrandrine, respectively. The functional studies showed that both alkaloids concentration‐dependently inhibited noradrenaline‐induced contraction in Ca 2+ ‐free solution (IC50 values, i.e. the concentrations needed to induce 50% inhibition, were 252.8 and 174.9 μM for tetrandrine and isotetrandrine, respectively), the spontaneous contractile response elicited by extracellular calcium after depletion of noradrenaline‐sensitive intracellular stores (increase in resting tone; IC50 values 11.6 and 19.6 μM for tetrandrine and isotetrandrine, respectively) and the refilling of intracellular Ca 2+ stores sensitive to noradrenaline (IC50 values 7.4 and 14.9 μM for tetrandrine and isotetrandrine, respectively). The results show that tetrandrine and isotetrandrine interact with α 1 ‐adrenoceptors by displacing the [ 3 H]prazosin binding site and that both compounds inhibit mainly the Ca 2+ ‐dependent process and have less action on α 1 ‐adrenoceptors. Tetrandrine is more potent than isotetrandrine.