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5-Hydroxytryptamine in PsychiatryA Spectrum of Ideas$
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Merton Sandler, Alec Coppen, and Sara Harnett

Print publication date: 1991

Print ISBN-13: 9780192620118

Published to Oxford Scholarship Online: March 2012

DOI: 10.1093/acprof:oso/9780192620118.001.0001

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

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

Chapter:
(p.43) 5. The inactive enantiomer of a noradrenaline uptake blocker reduces 5-HT synthesis
Source:
5-Hydroxytryptamine in Psychiatry
Author(s):

Peter C. Waldmeier

Laurent Maitre

Publisher:
Oxford University Press
DOI:10.1093/acprof:oso/9780192620118.003.0005

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

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