High-affinity [ 3H]desipramine binding in the peripheral and central nervous system: A specific site associated with the neuronal uptake of noradrenaline

Abstract

The specific binding of [ 3H]desipramine to various brain regions and peripheral tissues of the rat was of high affinity, rapid and reversible. It was inhibited with high affinity only by tricyclic antidepressants and noradrenaline uptake blockers. There was a highly significant correlation between the potencies of a series of drugs for the inhibition of [ 3H]desipramine binding and for the inhibition of noradrenaline uptake. Substrates for the noradrenaline uptake system however inhibited the binding of [ 3H]desipramine only at very high concentrations. Postganglionic sympathetic denervation of the submaxillary gland and the heart both resulted in a pronounced decrease in [ 3H]desipramine binding sites, which paralleled the reduction in endogenous noradrenaline levels. High-affinity [ 3H]desipramine binding sites thus appear to be localised on noradrenergic nerve endings and are probably closely associated with the neuronal uptake system for noradrenaline.