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Alpha-2 Adrenergic Receptor Sensitivity and the Mechanism of Action of Antidepressant Therapy

The Effect of Long-Term Amitriptyline Treatment

Published online by Cambridge University Press:  29 January 2018

Dennis S. Charney*
Affiliation:
Department of Psychiatry, Connecticut Mental Health Center, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508
George R. Heninger
Affiliation:
Department of Psychiatry, Connecticut Mental Health Center, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508
David E. Sternberg
Affiliation:
Department of Psychiatry, Connecticut Mental Health Center, Yale University School of Medicine, 34 Park Street, New Haven, CT 06508
*
Correspondence.

Summary

It has been hypothesized that the mechanism of action of antidepressant treatments is related to their ability to decrease the sensitivity of the alpha-2 adrenergic autoreceptor. In order to assess alpha-adrenergic autoreceptor sensitivity, the effects of clonidine, the alpha-2 adrenergic receptor agonist, on plasma levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenethyleneglycol (MHPG), blood pressure (BP) and patient-rated sedation were measured in nine depressed patients before and during amitripytline treatment. Postsynaptic alpha-2 adrenergic receptor sensitivity was assessed by determining the growth hormone (GH) response to clonidine before and during treatment. Amitriptyline significantly attenuated the effects of clonidine on plasma MHPG, standing systolic BP, and sedation, indicating that alpha-2 adrenergic autoreceptors had become subsensitive. In addition, baseline plasma MHPG levels were significantly reduced. Amitriptyline had no effect on the GH response to clonidine.

Type
Papers
Copyright
Copyright © 1983 The Royal College of Psychiatrists 

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