PMID: 10583Jan 1, 1976

Treatment of depression with tricyclic drugs--pharmacokinetic and pharmacodynamic aspects

Pharmakopsychiatrie, Neuro-Psychopharmakologie
M Asberg

Abstract

A series of studies on the pharmacokinetic and pharmacodynamic properties of some tricyclic antidepressants is reviewed. During treatment with the same oral dose of these drugs, patients develop widely differing plasma levels. The importance of this variability for the clinical effects has been studied in detail for the monomethylated compound, nortriptyline. There is an association between side-effects and high plasma levels of this drug. In endogenously depressed patients, the relationship between plasma level and effect appears to be curvilinear. The tricyclic antidepressants differ in their capacity to inhibit transmitter uptake into noradrenaline- and serotonin neurons respectively. Nortriptyline is a preferential noradrenaline uptake inhibitor, while the dimethylated compound, chlorimipramine also has a profound influence on serotonin neurons. These differential effects are also reflected in changes in the levels of the transmitter metabolites in cerebrospinal fluid (CSF). The CSF studies have also supported the hypothesis of a biochemical heterogeneity of the depressive syndrome. The levels of the serotonin metabolite, 5-HIAA were bimodally distributed in CSF. In patients with a low level of 5-HIAA there was a significan...Continue Reading

Related Concepts

Tricyclic Antidepressive Agents
Clomipramine Maleate (1: 1)
Depressive Symptoms
Homovanillic Acid
Hydroxyindoleacetic Acid
Methoxyhydroxyphenylglycol, (-)-Isomer
Neurons
Norepinephrine, (+, -)-Isomer
Norfenazin
Hydroxytryptamine

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