The inactive enantiomer of a noradrenaline uptake blocker reduces 5-HT synthesis

Peter C. Waldmeier and Laurent Maitre

in 5-Hydroxytryptamine in Psychiatry

Published in print February 1991 | ISBN: 9780192620118
Published online March 2012 | e-ISBN: 9780191724725 | DOI:
The inactive enantiomer of a noradrenaline uptake blocker reduces 5-HT synthesis

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The enantiomers of the tetracyclic antidepressant oxaprotiline differ in their ability to inhibit noradrenaline (NA) uptake. While (+)-oxaprotiline (CGP 12104 A) is extraordinarily potent in this respect, the (-)-enantiomer (CGP 12103 A, levoprotiline) is virtually inactive in vitro and in vivo. Levoprotiline was originally tested clinically in depressed patients as it is an ideal way to test the catecholamine hypothesis of affective disorders. Contrary to the prediction by this hypothesis, the compound clearly showed antidepressant effects in patients, which automatically raised the question of the mechanism of action. Levoprotiline has been found active in a number of behavioral tests for antidepressants: it was effective in the Porsolt swim test after chronic application; it enhanced the neurological syndrome induced by 5-hydroxytryptophan (5-HTP) and the stereotypies caused by apomorphine and after repeated treatment it also potentiated the effects of damphetamine and dopamine injected into the rat nucleus accumbens. Levoprotiline has little if any interaction with α2- and β-noradrenergic, cholinergic, serotonergic (5-HTx subtypes, 5-HT2), dopaminergic, GABAA, benzodiazepine, adenosine, and opiate receptors.

Keywords: enantiomers; tetracyclic antidepressant; norarenaline oxaprotiline; levoprotiline; swim test; apomorphine

Chapter.  2437 words.  Illustrated.

Subjects: Neuroscience

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