EFFECTS OF SOME ANTIDEPRESSANT DRUGS ON DEPLETION OF INTRANEURONAL BRAIN CATECHOLAMINE STORES CAUSED BY 4,ALPHA-DIMETHYL-META-TYRAMINE

Rats and mice were injected intraperitoneally with 4,α-dimethyl-meta-tyramine. As shown by histochemical (rats) and biochemical (mice) techniques this agent caused a decrease in catecholamine levels in central and peripheral (heart) noradrenaline and central dopamine neurons, accompanied by sympathomimetic stimulation and central excitation. These effects could be largely prevented by protriptyline and desipramine, previously found to be potent blockers of amine uptake by central and peripheral noradrenaline neurons. Dopamine neurons were resistant to the depletion-preventing action of these agents. Imipramine and amitriptyline showed slight, though significant activity in preventing depletion of central noradrenaline. In general the drugs were more potent in protecting peripheral than central noradrenaline stores. The results cast some doubt on the view that the antidepressant properties of thymoleptics are essentially due to inhibition of noradrenaline re-uptake at central synapses. Important components of the clinical action might well be due to other factors, e.g. a corresponding effect at central 5-hydroxytryptamine synapses. © 1969.