Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F15%3A00063456" target="_blank" >RIV/00159816:_____/15:00063456 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/15:00083475

Result on the web

<a href="https://www.jstage.jst.go.jp/article/tjem/236/3/236_199/_pdf" target="_blank" >https://www.jstage.jst.go.jp/article/tjem/236/3/236_199/_pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1620/tjem.236.199" target="_blank" >10.1620/tjem.236.199</a>

Result language

angličtina

Original language name

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts

Original language description

Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

ED - Physiology

OECD FORD branch

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Project

<a href="/en/project/ED1.100%2F02%2F0123" target="_blank" >ED1.100/02/0123: St. Anne´s University Hospital Brno - International Clinical Research Center (FNUSA-ICRC)</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Tohoku Journal Of Experimental Medicine

ISSN

0040-8727

e-ISSN

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Volume of the periodical

236

Issue of the periodical within the volume

3

Country of publishing house

JP - JAPAN

Number of pages

9

Pages from-to

199-207

UT code for WoS article

000358823400006

EID of the result in the Scopus database

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