Summary
Two methods have recently been described for determining the effect of psychotropic drugs on noradrenergic nerves. Membrane pump blockade can be quantified by inhibition of uptake of3H-noradrenaline (NA) by rat irides incubated in drug-containing plasma. Tyramine, an indirectly acting sympathomimetic, produces a temporary rise in blood pressure after intravenous injection and may also be used to quantify the effect of drugs on adrenergic transmitter mechanisms in man. Patients taking the neuroleptics, chlorpromazine, thioridazine and haloperidol have been studied. Using these two methods, haloperidol had no effect on noradrenergic transmitter mechanisms. Thioridazine also had no effect on the NA membrane pump but produced slight receptor blockade. Chlorpromazine had an inhibitory effect on the NA uptake mechanism of the rat iris, both in model experiments and in plasma from patients. The blockade was less than that produced by nortriptyline. The results of the tyramine test were similar to those obtained after nortriptyline. The discrepancy is probably due to blockade of the NA receptor by chlorpromazine.
The neuroleptic drugs appear to have in common the ability to produce blockade of central dopamine receptors and this has been proposed as the explanation of their antipsychotic effect. There is probably no simple relationship between the effects of these drugs on NA transmitter mechanisms and their antipsychotic effects. The widespread effects of chlorpromazine on monoamine transmitter mechanisms might, however, account for its continued popularity, often as the drug of choice, in treating psychoses, despite the introduction of many other neuroleptics.
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Tuck, J.R. Effects of chlorpromazine, thioridazine and haloperidol on adrenergic transmitter mechanisms in man. Eur J Clin Pharmacol 6, 81–87 (1973). https://doi.org/10.1007/BF00562431
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DOI: https://doi.org/10.1007/BF00562431