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Évolution des idées sur le mécanisme d'action des antidépresseurs : le concept d'hétéro-régulation des récepteurs

Published online by Cambridge University Press:  28 April 2020

J.P. Tassin
J.P. Tassin*
Affiliation:
Chaire de Neuropharmacologie, INSERM U.114, Collège de France - 75231, PARIS CÉDEX 05
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Résumé

Des lès premières années d'utilisation clinique des antidépresseurs, les neurones à sérotonine (5-HT) et à noradrénaline (NA) ont été considérés comme les sites d'action privilégiés de ces médicaments.

En vingt ans, les idées sur leurs mécanismes d'action ont évolué parallèlement à la progression des connaissances et à l'obtention de nouvelles molécules actives :

  • - Tout d'abord, les effets présynaptiques des traitements aigus (inhibition des monoamines oxydases et inhibition de la recapture des monoamines par les antidépresseurs tricycliques) ont paru expliquer l'effet clinique de ces substances.

  • - Plus tard, les effets post-synaptiques des traitements chroniques (désensibilisation des récepteurs β-adrénergiques et, dans la plupart des cas, la désensibilisation des récepteurs 5-HT2) se sont avérés être une action biochimique commune de ces traitements.

  • - Récemment, les effets synaptiques homologues - en l'occurrence la desensibilisation des récepteurs α2-adrénergiques - ont été considérés comme un préalable à la désensibilisation des récepteurs β-adrénergiques post-synaptiques.

  • - Enfin, les effets synaptiques hétérologies sont proposés comme pouvant rendre compte de Taction clinique des antidépresseurs.

C'est la stimulation - directe ou indirecte - des récepteurs sérotoninergiques (5-HT2) qui serait nécessaire à l'obtention d'un découplage β lors d'une stimulation des récepteurs β-adrénergiques.

Les molécules antidepressives n'auraient d'action thérapeutique qu'à condition d'agir de façon synergique sur les transmissions sérotoninergique et noradrénergique.

Summary

Summary

During the first years of clinical use of anti-depressants, serotonergic (5-HT) as well as noradrenergic (NA) neurons were considered as the privileged sites of action of these drugs.

For the last twenty years, ideas on their mechanism of action have progressed in parallel with an increased scientific knowledge and the availability of new active molecules.

- First, the presynaptic effects of acute treatments (monoamine oxidases inhibition and inhibition of the monoamine reuptake by tricyclic anti-depressants) seemed to explain the clinical effect of these substances.

- Later, the postsynaptic effects of chronic treatments (desensitization of β-adrenergic receptors and, in most cases, the desensitization of 5-HT2 receptors) were considered as being the common biochemical sites of these treatments.

- Recently, the effects on homologous synapses - i.e. the desensitization of the α2 adrenergic receptors - seemed to be necessary for the further desensitization of the postsynaptic β-adrenergic receptors.

- Finally, the effects on heterologous synapses are proposed as sustaining the clinical action of anti-depressants.

It is the stimulation - direct or indirect - of serotonergic receptors (5-HT2) which would be necessary to obtain the uncoupling of the β-receptors following their hyperstimulation.

The anti-depressive molecules would not, therefore, perform their therapeutic effect without acting in a synergistic manner on serotonergic and noradrenergic transmissions.

Keywords

AntidépresseursRécepteurs sérotoninergiquesRécepteurs noradrénergiquesHétéro-régulation des récepteurs
Type
Research Article
Information
Psychiatry and Psychobiology , Volume 1 , Issue 1 , 1986 , pp. 62 - 74
Copyright
Copyright © European Psychiatric Association 1986

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