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.