Molecular mechanisms of the reversal of imipramine-induced sodium channel blockade by alkalinization in human cardiac myocytes

Bou-Abboud, Elias; Nattel, Stanley

doi:10.1016/s0008-6363(98)00011-x

Cited by 32 publications

(11 citation statements)

References 31 publications

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“…The potency of tricyclic antidepressants as sodium channel inhibitors was shown by the low micromolar IC 50 values in vitro (e.g., Bou-Abboud and Nattel, 1998;Nicholson et al, 2002;Pancrazio et al, 1998), and by their in vivo efficiency against neuropathic pain (Namaka et al, 2004).…”

mentioning

confidence: 99%

The Mechanism of Activity-Dependent Sodium Channel Inhibition by the Antidepressants Fluoxetine and Desipramine

et al. 2006

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The effect of monoamine uptake inhibitor-type antidepressants on sodium channels of hippocampal neurons was investigated. Members of the tricyclic group of antidepressants are known to modify multiple targets, including sodium channels, whereas selective serotonin-reuptake inhibitors (SSRIs) are regarded as highly selective compounds, and their effect on sodium channels was not investigated in detail. In this study, a representative member of each group was chosen: the tricyclic antidepressant desipramine and the SSRI fluoxetine. The drugs were roughly equipotent use-dependent inhibitors of sodium channels, with IC 50 values ϳ100 M at Ϫ150 mV holding potential, and ϳ1 M at Ϫ60 mV. We suggest that therapeutic concentrations of antidepressants affect neuronal information processing partly by direct, activity-dependent inhibition of sodium channels. As for the mechanism of inhibition, use-dependent inhibition by antidepressants was believed to be due to a preferential affinity to the fast-inactivated state. Using a voltage and perfusion protocol by which relative affinities to fast-versus slow-inactivated states could be assessed, we challenged this view and found that the affinity of both drugs to slowinactivated state(s) was higher. We propose a different mechanism of action for these antidepressants, in which slow rather than fast inactivation plays the dominant role. This mechanism is similar but not equivalent with the novel mechanism of usedependent sodium channel inhibition previously described by our group (Neuroscience

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confidence: 99%

The Mechanism of Activity-Dependent Sodium Channel Inhibition by the Antidepressants Fluoxetine and Desipramine

et al. 2006

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“…In vitro studies have demonstrated that sodium bicarbonate can increase Vmax which should correspond to a decrease in the time of phase 0 of the action potential. In addition, there are in vitro and animal studies that favor alkalosis and hypertonic sodium loading separately and in combination [38,40,41,64]. Human case reports and series on treating TCA poisoning with sodium bicarbonate began in the 1970s [58,60].…”

Section: Antidepressantsmentioning

confidence: 99%

“…Case reports [1,3,53,54] Cocaine Case reports [6,7,55,56] C a n i n e [ 42,57] Cyclic antidepressants Case reports, retrospective series [19,50,58,59] Canine, rat, swine [41,[60][61][62][63] Canine Purkinje fibers, human atrial myocytes [64] Diphenhydramine Case report [2,65] Flecainide Case reports [8,66] …”

Section: Other Sodium Channel Blocking Agentsmentioning

confidence: 99%

A Literature Review of the Use of Sodium Bicarbonate for the Treatment of QRS Widening

Bruccoleri

Burns

2015

J. Med. Toxicol.

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Sodium bicarbonate is a well-known antidote for tricyclic antidepressant (TCA) poisoning. It has been used for over half a century to treat toxin-induced sodium channel blockade as evidenced by QRS widening on the electrocardiogram (ECG). The purpose of this review is to describe the literature regarding electrophysiological mechanisms and clinical use of this antidote after poisoning by tricyclic antidepressants and other agents. This article will also address the literature supporting an increased serum sodium concentration, alkalemia, or the combination of both as the responsible mechanism(s) for sodium bicarbonate's antidotal properties. While sodium bicarbonate has been used as a treatment for cardiac sodium channel blockade for multiple other agents including citalopram, cocaine, flecainide, diphenhydramine, propoxyphene, and lamotrigine, it has uncertain efficacy with bupropion, propranolol, and taxine-containing plants.

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“…9 Second, alkalinization also promotes the disassociation of the tricyclic medication from cardiac sodium channels and decreases the TCA-induced blockade, which is the primary cause of arrhythmias. 10 Finally, the increase in extracellular sodium levels may help compensate for the inhibition of cardiac channels by creating a larger concentration gradient and allowing a larger influx of sodium, restoring function. 11 Benzodiazepines are the treatment of choice for patients who present with seizures.…”

Section: Tricyclic Antidepressantsmentioning

confidence: 99%

Suspected Tricyclic Antidepressant Overdose Successfully Treated With Lipids

Perza

Schneider²,

Rosini³

2013

Journal of Emergency Nursing

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Molecular mechanisms of the reversal of imipramine-induced sodium channel blockade by alkalinization in human cardiac myocytes

Cited by 32 publications

References 31 publications

The Mechanism of Activity-Dependent Sodium Channel Inhibition by the Antidepressants Fluoxetine and Desipramine

The Mechanism of Activity-Dependent Sodium Channel Inhibition by the Antidepressants Fluoxetine and Desipramine

A Literature Review of the Use of Sodium Bicarbonate for the Treatment of QRS Widening

Suspected Tricyclic Antidepressant Overdose Successfully Treated With Lipids

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