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PubMed · 1141399

Sensitive method for the routine determination tricyclic antidepressants in plasma using a specific nitrogen detector.

L A Gifford·P Turner·C M Pare
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Abstract

The sensitivity of the alkali flame ionization detector to the tricyclic antidepressant drugs has been studied and limits of detection measured. A backflush system has been used to enable measurement in plasma extracts. A general method for the estimation of tricyclic plasma levels has been developed and exemplified by the measurement of imipramine at therapeutic levels.

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Antidepressive Agents, TricyclicChromatography, GasDose-Response Relationship, DrugDrug StabilityHumansImipramineMethodsNitrogenJournal Article

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L A Gifford, P Turner, C M Pare. 1975-02-19. Sensitive method for the routine determination tricyclic antidepressants in plasma using a specific nitrogen detector.. https://doi.org/10.1016/s0021-9673(01)81094-3

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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↗