Escitalopram, a selective serotonin reuptake inhibitor, inhibits voltage-dependent K<sup>+</sup>channels in coronary arterial smooth muscle cells

Kim, Han Sol; Li, Hongliang; Kim, Hye Won; Shin, Seungjae; Seo, Mi Seon; An, Jin Ryeol; Ha, Kwon‐Soo; Han, Eun‐Taek; Hong, Seok‐Ho; Choi, Il‐Whan; Choi, Grace; Lee, Daesung; Park, Won Sun

doi:10.4196/kjpp.2017.21.4.415

Cited by 17 publications

(13 citation statements)

References 28 publications

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“…In particular, augmentation of Notch1 activity may play a role in the effects seen in our disease models. Sertraline (25) and escitalopram (26) have been shown to inhibit voltage-dependent K+ channel activity in smooth muscle cells, suggesting another potential mechanism to be investigated in a future study. It is notable that serotonin treatment did not rescue the drpr-deficient flies, suggesting that the mechanism of action of sertraline in this context is independent of effects on serotonin activity.…”

Section: Discussionmentioning

confidence: 99%

Selective serotonin reuptake inhibitors ameliorate MEGF10 myopathy

Saha

Rizzo

Ramanathan

et al. 2019

Human Molecular Genetics

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MEGF10 myopathy is a rare inherited muscle disease that is named after the causative gene, MEGF10. The classic phenotype, early onset myopathy, areflexia, respiratory distress and dysphagia, is severe and immediately life-threatening. There are no disease-modifying therapies. We performed a small molecule screen and follow-up studies to seek a novel therapy. A primary in vitro drug screen assessed cellular proliferation patterns in Megf10-deficient myoblasts. Secondary evaluations were performed on primary screen hits using myoblasts derived from Megf10−/− mice, induced pluripotent stem cell-derived myoblasts from MEGF10 myopathy patients, mutant Drosophila that are deficient in the homologue of MEGF10 (Drpr) and megf10 mutant zebrafish. The screen yielded two promising candidates that are both selective serotonin reuptake inhibitors (SSRIs), sertraline and escitalopram. In depth follow-up analyses demonstrated that sertraline was highly effective in alleviating abnormalities across multiple models of the disease including mouse myoblast, human myoblast, Drosophila and zebrafish models. Sertraline also restored deficiencies of Notch1 in disease models. We conclude that SSRIs show promise as potential therapeutic compounds for MEGF10 myopathy, especially sertraline. The mechanism of action may involve the Notch pathway.

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Section: Discussionmentioning

confidence: 99%

Selective serotonin reuptake inhibitors ameliorate MEGF10 myopathy

Saha

Rizzo

Ramanathan

et al. 2019

Human Molecular Genetics

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“…The studies conducted on animal models have shown that fluoxetine causes dilatation of cerebral arterioles and skeletal muscle arterioles, as well as inhibition of the potassium‐induced contraction of the isolated uterine artery . A group of authors from South Korea showed that escitalopram, sertraline, and fluvoxamine cause dose‐dependent inhibition of voltage‐dependent potassium channels and consequent vasoconstriction in coronary arterial smooth muscle cells of rabbits. On the other hand, in the same studies paroxetine did not affect the contractility of coronary smooth muscle cells.…”

Section: Discussionmentioning

confidence: 99%

“…'vreme' = time in seconds shown that fluoxetine causes dilatation of cerebral arterioles 15 and skeletal muscle arterioles, 16 as well as inhibition of the potassiuminduced contraction of the isolated uterine artery. 16 A group of authors from South Korea showed that escitalopram, 10 with the current state of knowledge. Paroxetine was found to have contractile effects on guinea-pig urethra, while other SSRIs did not, 17 and citalopram was the only SSRI that did not inhibit acetylcholineinduced contractions of guinea-pig urinary bladder, 18 suggesting outstanding pro-contractile effect of these two drugs on smooth muscles; but we cannot progress further from these observations when trying to understand selectivity of their action on contractility of the fallopian tube ampulla and isthmus.…”

Section: Discussionmentioning

confidence: 99%

“…Fluoxetine also causes dose‐dependent contractions of smooth muscle cells from the stomach, in the first place of cells localized in the fundus, followed by those in antral and pyloric part; possible mechanisms of the fluoxetine action involve interaction with a muscarinic, α‐adrenergic and serotonergic receptors on membranes of the smooth muscle cells . Recent studies have shown that escitalopram, sertraline, and fluvoxamine inhibit potassium channels on the smooth muscle cells from the coronary arteries, reducing the amplitude of potassium ion currents.…”

Section: Introductionmentioning

confidence: 99%

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Effects of selective serotonin reuptake inhibitors on motility of isolated fallopian tube

Milosavljević

Janković

Djuric

et al. 2019

Clin Exp Pharma Physio

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Selective serotonin reuptake inhibitors (SSRIs) affect the smooth muscle cells acting on voltage‐dependent channels for Na+, K+ and Ca2+, but their action is tissue and species specific. The aim of our study was to investigate effects of selective serotonin reuptake inhibitors on motility of the isolated fallopian tubes. Isolated preparations of isthmus and ampoule were taken from fallopian tubes of 20 women during hysterectomy due to uterine fibroids and then tested for reactivity on increasing concentrations of selective serotonin reuptake inhibitors. Escitalopram (from 0.9 × 10−9 M/L to 1.4 × 10−6 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated ampulla (EC50 = 1.20 ± 1.06 × 10−8 M/L, r = 0.580, P < 0.05) (F = 2.980, df1 = 6, df2 = 28, P < 0.05). Paroxetine (from 1.2 × 10−9 M/L to 5.1 × 10−5 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated isthmus (EC50 = 7.01 ± 3.50 × 10−8 M/L, r = 0.500, P < 0.05) (F = 2.350, df1 = 9, df2 = 40, P < 0.05). The SSRIs differ among themselves in regard to their potential to affect motility of the fallopian tubes. Escitalopram and paroxetine have clear stimulating effect which may interfere with functioning of the fallopian tubes, and potentially impair fertility if taken by women in reproductive period of life. The other SSRIs tested in the study did not produce significant effect throughout the concentration range used in the experiments.

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“…For this reason, the adverse effects of some drugs on vascular Kv channels should be investigated to avoid misinterpretation of clinical/experimental data regarding vascular function. To date, various drugs and chemicals have been reported to inhibit vascular Kv channels independently of their intrinsic functions [ 22 23 ]. Our group recently reported the direct effect of amiodarone, a class III antiarrhythmic drug, on vascular Kv channels using coronary arterial smooth muscle cells [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of voltage-dependent K⁺ current in rabbit coronary arterial smooth muscle cells by the class Ic antiarrhythmic drug propafenone

Seo

et al. 2018

Korean J Physiol Pharmacol

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In this study, we demonstrated the inhibitory effect of the Class Ic antiarrhythmic agent propafenone on voltage-dependent K+ (Kv) channels using freshly isolated coronary artery smooth muscle cells from rabbits. The Kv current amplitude was progressively inhibited by propafenone in a dose-dependent manner, with an apparent IC50 value of 5.04±1.05 µM and a Hill coefficient of 0.78±0.06. The application of propafenone had no significant effect on the steady-state activation and inactivation curves, indicating that propafenone did not affect the voltage-sensitivity of Kv channels. The application of train pulses at frequencies of 1 or 2 Hz progressively increased the propafenone-induced inhibition of the Kv current. Furthermore, the inactivation recovery time constant was increased after the application of propafenone, suggesting that the inhibitory action of propafenone on Kv current is partially use-dependent. Pretreatment with Kv1.5, Kv2.1 or Kv7 inhibitor did not change the inhibitory effect of propafenone on the Kv current. Together, these results suggest that propafenone inhibits the vascular Kv channels in a dose- and use-dependent manner, regardless of Na+ channel inhibition.

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Escitalopram, a selective serotonin reuptake inhibitor, inhibits voltage-dependent K⁺channels in coronary arterial smooth muscle cells

Cited by 17 publications

References 28 publications

Selective serotonin reuptake inhibitors ameliorate MEGF10 myopathy

Selective serotonin reuptake inhibitors ameliorate MEGF10 myopathy

Effects of selective serotonin reuptake inhibitors on motility of isolated fallopian tube

Inhibition of voltage-dependent K⁺ current in rabbit coronary arterial smooth muscle cells by the class Ic antiarrhythmic drug propafenone

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Escitalopram, a selective serotonin reuptake inhibitor, inhibits voltage-dependent K+channels in coronary arterial smooth muscle cells

Cited by 17 publications

References 28 publications

Selective serotonin reuptake inhibitors ameliorate MEGF10 myopathy

Selective serotonin reuptake inhibitors ameliorate MEGF10 myopathy

Effects of selective serotonin reuptake inhibitors on motility of isolated fallopian tube

Inhibition of voltage-dependent K+ current in rabbit coronary arterial smooth muscle cells by the class Ic antiarrhythmic drug propafenone

Contact Info

Product

Resources

About

Escitalopram, a selective serotonin reuptake inhibitor, inhibits voltage-dependent K⁺channels in coronary arterial smooth muscle cells

Inhibition of voltage-dependent K⁺ current in rabbit coronary arterial smooth muscle cells by the class Ic antiarrhythmic drug propafenone