Cardiac electrophysiology of four neuroleptics: Melperone, haloperidol, thioridazine and chlorpromazine

Arlock, Per; Gullberg, Bo; Olsson, Sven-Olle

doi:10.1007/bf00501374

Cited by 31 publications

(10 citation statements)

References 51 publications

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“…In our experiments, 1 μmol/l of haloperidol suppressed cardiac action potential up to its complete inhibition. This observation is similar to that reported by Arlock et al (1978) for isolated guinea-pig papillary muscle in which 10 μmol/l of haloperidol caused decrease in APD 50 and decrease in action potential amplitude. Nevertheless, the same author (Arlock et al 1978) reported also widening of action potential length by low haloperidol concentrations.…”

Section: Discussionsupporting

confidence: 81%

“…In isolated guinea-pig papillary muscle, 1 μmol/l haloperidol prolonged and 10 μmol/l shortened the action potential duration (Arlock et al 1978). In anesthetized dogs haloperidol consistently prolonged the repolarization phase of an action potential recorded by monophasic action potential catheters (Sugiyama et al 2001;Rasty et al 2004).…”

Section: Introductionmentioning

confidence: 99%

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Haloperidol moderately inhibits cardiovascular L-type calcium current

Tarabová

Novàkovâ²,

Lacinová³

2009

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Abstract. Effects of haloperidol on L-type Ca V 1.2 channel were studied. Calcium current was measured in whole cell patch-clamp using calcium as a charge carrier. Inhibition by haloperidol was investigated in Ca V 1.2 channel natively expressed in rat cardiac myocytes and recombinant cardiac (Ca V 1.2 a ) and vascular (Ca V 1.2 b ) splice variants of the channel expressed in HEK 293 cells. Haloperidol inhibited L-type calcium current in a concentration-dependent manner with a threshold of 1 nmol/l. 1 μmol/l haloperidol inhibited 20.6 ± 3.6% of calcium current amplitude in cardiomyocytes, 25.4 ± 2.6% of current amplitude through the Ca V 1.2 b channel and 28.0 ± 2.7% of current through the Ca V 1.2 a channel. Inhibition was not accompanied by alteration of current waveform or by shift of current-voltage relation. In a current clamp haloperidol suppressed action potential generation. 1 μmol/l of the drug shortened the action potential duration in part of the cells and suppressed fully action potential in other cells. Moderate inhibition of the L-type calcium channels by haloperidol might cause shortening of action potential. Complete abolishment of action potential must have been mediated by inhibition of another, likely sodium channel.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Haloperidol moderately inhibits cardiovascular L-type calcium current

Tarabová

Novàkovâ²,

Lacinová³

2009

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“…For instance, melperone is an a-adrenoceptor blocking agent (Peterson, 1981) and it prolongs the duration of the cardiac action potential (Arlock, 1978). Both of these actions may contribute to the marked protection against reperfusion-induced arrhythmias since drugs with similar properties such as prazosin (Sheridan etal., 1980) and amiodarone (Lubbe etal., 1979) have also been reported to be effective.…”

Section: Discussionmentioning

confidence: 99%

An investigation into the characteristics of reperfusion‐induced arrhythmias in the anaesthetized rat and their susceptibility to antiarrhythmic agents

Kane

Parratt

Williams

1984

British J Pharmacology

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1Reperfusion-induced arrhythmias were elicited in the pentobarbitone-anaesthetized rat by occlusion of the left main coronary artery and subsequent release. 2 These arrhythmias were rapid in onset, occurring within 20 s after release of the ligature, and were of short duration (1 -2 min). Their severity was dependent upon the duration of the preceding occlusion. A 5 or 15 min occlusion period produced the most severe arrhythmias on release, the incidence of ventricular fibrillation being 56 and 50% respectively. 3 Evidence that reperfusion had occurred was provided by fluorescein dye distribution and intramyocardial temperature studies. 4 The severity of reperfusion arrhythmias and mortality was unaffected by bilateral vagotomy, P-adrenoceptor blockade by atenolol (2 mg kg-' i.v.) or a combination of the two. The incidence of reperfusion-induced ventricular fibrillation was significantly reduced by Org 6001 (which blocks the fast inward sodium current), melperone (which acutely prolongs the cardiac action potential duration) and bepridil (which blocks both fast and slow inward currents). It was unaffected by nitroglycerine and the calcium antagonists verapamil, prenylamine and nifedipine. 6 We have shown that reperfusion-induced cardiac arrhythmias can be consistently elicited in the anaesthetized rat and that they are particularly susceptible to drugs that can block the fast inward sodium current.

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“…Melperone, a neuroleptic butyrophenone, has been shown to possess antiarrhythmic properties in vitro (Arlock et al, 1978) and in vivo (Petersen, 1978;, including clinical efficacy in acute myocardial infarction (M0gelvang et al, 1980). It was reported that in mammalian cardiac muscles, melperone prolonged the action potential duration (APD) and the effective refractory period (ERP) without affecting the maximum rate of depolarization (J,,.,) and without depressing contractility (Millar & Vaughan Williams, 1982).…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological effects of melperone on isolated rabbit heart muscles

Ikeguchi

Hashimoto

Horie

et al. 1988

British J Pharmacology

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1 Electrophysiological effects of melperone on isolated atrial and ventricular muscle preparations of the rabbit were studied by a conventional microelectrode technique. 2 Melperone (3.3 pM) prolonged the action potential duration and effective refractory period of the atrial preparations without affecting the maximum rate of depolarization (V,,) These effects of melperone on action potential duration and effective refractory period were inhibited by a low potassium perfusate (2.7 mM).3 A high concentration of melperone (16.6 gM) decreased P. of atrial preparations. In ventricular muscles, melperone at either concentration decreased P..., although the increase in action potential duration was greater than in the atrium. 4 Depression of ft.,, of ventricular muscles by melperone was found to be augmented by an increase of stimulation frequency and drug concentration. 5 The rate of onset of rate-dependent block of f,,., in ventricle was increased with drug concentration and frequency of stimulation. However, the time constant of recovery from rate-dependent block was almost constant. The kinetics of rate-dependent block of P.,, by melperone were approximately similar to those of quinidine and disopyramide. Consequently it is concluded that melperone possesses class la antiarrhythmic activity as well as class 3 activity.

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Cardiac electrophysiology of four neuroleptics: Melperone, haloperidol, thioridazine and chlorpromazine

Cited by 31 publications

References 51 publications

Haloperidol moderately inhibits cardiovascular L-type calcium current

Haloperidol moderately inhibits cardiovascular L-type calcium current

An investigation into the characteristics of reperfusion‐induced arrhythmias in the anaesthetized rat and their susceptibility to antiarrhythmic agents

Electrophysiological effects of melperone on isolated rabbit heart muscles

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