Serotonergic and noradrenergic reuptake inhibitors: Prediction of clinical effects from in vitro potencies

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

This article reviews the pharmacology of antidepressants, particularly focusing on those that act acutely by blocking the reuptake of norepinephrine (NE) and/or serotonin (5-HT). Such drugs have a very wide range of potencies, measured in vitro, to inhibit the reuptake of these biogenic amines. As a group, the selective serotonin reuptake inhibitors (SSRIs) are the most potent at inhibiting the reuptake of 5-HT. Some tricyclic antidepressants (TCAs), such as desipramine and nortriptyline, are much more potent at blocking NE reuptake than 5-HT reuptake, as is the new non-TCA drug reboxetine. Among SSRIs, paroxetine is most potent at blocking the reuptake of NE. When considering whether such potencies measured in vitro translate into pharmacologic effects clinically, it is necessary to know how much drug gets to its site of therapeutic action, presumably the brain. Most, but not all, antidepressants are extensively bound to plasma proteins, and this binding limits considerably the penetration of these drugs across the blood-brain barrier. The amount of drug present in the extracellular fluid (ECF) of brain approximates the non-protein-bound drug concentration in plasma. Comparison of the concentration of antidepressants in ECF with their potencies to inhibit the reuptake of 5-HT and/or NE reveals why some drugs block the reuptake of these biogenic amines in either a selective or nonselective manner. This analysis reveals that venlafaxine may be unique among antidepressants in having a dose-dependent nonselectivity; at low doses it acts primarily as an SSRI, but at higher doses it inhibits the reuptake of NE as well.

Original languageEnglish (US)
Pages (from-to)16-23
Number of pages8
JournalJournal of Clinical Psychiatry
Volume62
Issue numberSUPPL. 12
StatePublished - 2001

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Antidepressive Agents
Serotonin
Norepinephrine
Serotonin Uptake Inhibitors
Pharmaceutical Preparations
Biogenic Amines
Extracellular Fluid
Nortriptyline
Paroxetine
Desipramine
Tricyclic Antidepressive Agents
Brain
Blood-Brain Barrier
Protein Binding
In Vitro Techniques
Blood Proteins
Pharmacology
Therapeutics

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Clinical Psychology

Cite this

Serotonergic and noradrenergic reuptake inhibitors : Prediction of clinical effects from in vitro potencies. / Frazer, Alan.

In: Journal of Clinical Psychiatry, Vol. 62, No. SUPPL. 12, 2001, p. 16-23.

Research output: Contribution to journalArticle

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