Document Detail


The role of alpha 2-adrenoceptors in the mechanism of action of antidepressant drugs.
MedLine Citation:
PMID:  2847126     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic treatment of rats with imipramine or electroconvulsive shock evokes a significant decrease in binding of [3H]-clonidine to homogenates from the rat brain cerebral cortex. The decrease in binding is accompanied with a functional hyposensitivity of alpha 2-adrenoceptors as measured by attenuation of several central effects of clonidine (e.g. attenuation of clonidine-induced hypothermia, sedation, inhibition of noradrenaline formation). The influence of these antidepressants on alpha 2-adrenoceptors may be of importance in the context of data showing that prolonged treatment with these drugs attenuates the cAMP formation after noradrenergic stimulation, and that the alpha 2-adrenoceptors together with beta-adrenoceptors contribute to the formation of the second messenger. The prolonged administration of imipramine and electroshock, as well as other antidepressant treatments, e.g. administration of the monoamine oxidase inhibitor pargyline or atypical antidepressants such as trazodone, mianserin citalopram, fluoxetine, inhibit the interaction between beta- and-alpha-adrenoceptors (with the alpha 2-subtype playing a major role) and may thus contribute to the phenomenon known as the beta-adrenoceptor down-regulation. The inhibition of the interaction between alpha and beta-adrenoceptors by antidepressants may occur in multiple ways: 1. by lowering the number of beta-adrenoceptors; 2. by lowering the number of alpha 2-receptors (e.g. after imipramine or ETC); 3. by a shift of alpha 2 receptors to a higher affinity state, which represents a desensitized form of the receptor (e.g. decrease in Kd after imipramine or citalopram); 4. by a shift to an antagonist preferring state of the receptor (e.g. after treatment with fluoxetine or trazodone); 5. by a combination of the mentioned above. The functional interaction between alpha and beta adrenoceptors is presumably not dependent upon the integrity of the noradrenergic system, as it not only occurs but also is enhanced in reserpinized or 6OHDA treated rats.
Authors:
A Pilc
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Polish journal of pharmacology and pharmacy     Volume:  39     ISSN:  0301-0244     ISO Abbreviation:  Pol J Pharmacol Pharm     Publication Date:    1987 Nov-Dec
Date Detail:
Created Date:  1988-12-06     Completed Date:  1988-12-06     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  0366561     Medline TA:  Pol J Pharmacol Pharm     Country:  POLAND    
Other Details:
Languages:  eng     Pagination:  691-713     Citation Subset:  IM    
Affiliation:
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antidepressive Agents / pharmacology*
Receptors, Adrenergic, alpha / physiology*
Chemical
Reg. No./Substance:
0/Antidepressive Agents; 0/Receptors, Adrenergic, alpha

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