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PubMed · 6478050

[Tricyclic antidepressive agents].

D Ginestet
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Abstract

The tricyclic antidepressive agents are still the drugs of choice because of their reliable action and the percentage of successes obtained (60 to 75%), especially in major depressions with deep melancholia. The course of antidepressive drugs is well documented, any depression needs at least three to four months' maintenance treatment after an initial phase of one month's treatment, frequently intravenous treatment is required. Current research is aimed at providing tricyclic agents without anticholinergic activity, the cause of most of their undesirable side-effects.

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Antidepressive Agents, TricyclicDepressive DisorderHumansEnglish AbstractJournal Article

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BibTeXRIS

D Ginestet. 1984. [Tricyclic antidepressive agents].. https://pubmed.ncbi.nlm.nih.gov/6478050/

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PubMed2006

Inhibition of astroglial inwardly rectifying Kir4.1 channels by a tricyclic antidepressant, nortriptyline.

The inwardly rectifying K(+) (Kir) channel Kir4.1 is responsible for astroglial K(+) buffering. We examined the effects of nortriptyline, a tricyclic antidepressant (TCA), on Kir4.1 channel currents heterologously expressed in HEK293T cells, using a whole-cell patch-clamp technique. Nortriptyline (3-300 microM) reversibly inhibited Kir4.1 currents in a concentration-dependent manner, whereas it marginally affected neuronal Kir2.1 currents. The inhibition of Kir4.1 channels by nortriptyline depended on the voltage difference from the K(+) equilibrium potential (E(K)), with greater potency at more positive potentials. Blocking kinetics of the drug could be described by first-order kinetics, where dissociation of the drug slowed down and association accelerated as the membrane was depolarized. The dissociation constant (K(d)) of nortriptyline for Kir4.1 inhibition was 28.1 microM at E(K). Other TCAs, such as amitriptyline, desipramine, and imipramine, also inhibited Kir4.1 currents in a similar voltage-dependent fashion. This study shows for the first time that nortriptyline and related TCAs cause a concentration-, voltage-, and time-dependent inhibition of astroglial K(+)-buffering Kir4.1 channels, which might be involved in therapeutic and/or adverse actions of the drugs.

Antidepressive Agents, Tricyclic↗