Iloperidone (Fanapt®), a novel atypical antipsychotic, is a potent HERG blocker and delays cardiac ventricular repolarization at clinically relevant concentration

Vigneault, Patrick; Pilote, Sylvie; Patoine, Dany; Simard, Chantale; Drolet, Benoît

doi:10.1016/j.phrs.2012.03.008

Cited by 13 publications

(13 citation statements)

References 20 publications

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“…2 Animal studies reveal similar findings, but with a maximal prolongation observed even at very high doses (3 mg/kg caused a maximal QTc 42.7 ± 10.2 ms prolongation in guinea pig hearts). 4 Iloperidone is a potent inhibitor of the hERG protein (human Ether-à-go-go-Related Gene), a subunit of the potassium channel that mediates the inwardly repolarizing potassium current; so as the drug concentration increases, repolarization is delayed and QTc is prolonged. 4 For this individual, his post ingestion course appears to be similar to the cases reported to the FDA (Table 1): with QTc prolongation without arrhythmia or hypotension, tachycardia, or sedation.…”

Section: Discussionmentioning

confidence: 99%

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A case of iloperidone overdose in a 27-year-old man with cocaine abuse

Amon

Stephen

El‐Mallakh

2016

SAGE Open Medical Case Reports

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Introduction:Iloperidone is a recently introduced antipsychotic medication. It is approved for the treatment of schizophrenia. There are no published reports of iloperidone overdosage, but there are eight cases that have been reported to the US Food and Drug Administration.Case report:A case of a 27-year-old man who took 84 mg of iloperidone while also smoking cocaine is described. He developed a prolonged QTc (527 ms) without arrhythmias and respiratory failure with mandated respiratory support. He ultimately recovered without sequelae.Discussion:The information regarding previous cases of toxicity on the US Food and Drug Administration website is incomplete. However, there were no fatalities due to iloperidone over-ingestion. Prolongation of the QTc may be a common feature.

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Section: Discussionmentioning

confidence: 99%

“…4 Iloperidone is a potent inhibitor of the hERG protein ( h uman E ther-à-go-go - R elated G ene), a subunit of the potassium channel that mediates the inwardly repolarizing potassium current; so as the drug concentration increases, repolarization is delayed and QTc is prolonged. 4…”

Section: Discussionmentioning

confidence: 99%

A case of iloperidone overdose in a 27-year-old man with cocaine abuse

Amon

Stephen

El‐Mallakh

2016

SAGE Open Medical Case Reports

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“…A preclinical study[3] demonstrated that iloperidone delays cardiac repolarization. A review[4] observed that no deaths or serious arrhythmias attributable to QTc prolongation had occurred in any of the iloperidone clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…We suggest two important reasons why iloperidone was likely responsible for the VPCs. First, iloperidone not only inhibits cardiac repolarization[3] but also potently blocks alpha 2c receptors;[6] the latter pharmacodynamic action may have a cardiostimulatory effect, explaining the VPCs. Next, the onset and offset of VPCs were temporally related with the onset and offset of iloperidone treatment.…”

Section: Discussionmentioning

confidence: 99%

Ventricular premature contractions associated with iloperidone

Achalia

Andrade

2013

Indian J Psychiatry

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Typical and atypical antipsychotic drugs are known to block potassium repolarization channels, prolong the QTc interval, and thereby predispose to ventricular tachyarrhythmias. We report a young male schizophrenic patient who experienced clinically significant and symptomatically distressing ventricular premature contractions (VPCs) in close temporal relation with iloperidone (8-16 mg/day) treatment; there had been no VPCs with prior exposure to risperidone, trihexyphenidyl, and olanzapine, nor with subsequent exposure to asenapine. We hypothesize that the VPCs may have been triggered by an alpha 2c receptor blockade-mediated cardiostimulatory action associated with iloperidone.

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“…The Langendorff retroperfusion installation and experimental procedures were fully described previously. 13 After monophasic action potentials (MAPs) were recorded at baseline, perfusion was performed for 15 minutes with buffer containing remdesivir (MedKoo Biosciences Inc, Morrisville, NC) at concentrations of 3 µmol/L (n = 7 hearts), 10 µmol/L (n = 8 hearts), or 30 µmol/L (n = 8 hearts). As the C max observed after the administration of the first 200 mg dose of remdesivir in humans was found to be 9 µmol/L, 14 we chose to assess the ex vivo effects of the drug at 3, 10, and 30 µmol/L, which fairly correspond to the human C max : (10 µmol/L), 3 times less: (3 µmol/L), and 3 times more: (30 µmol/L).…”

Section: Methodsmentioning

confidence: 99%

Remdesivir (VEKLURY) for treating COVID-19: Guinea pig ex vivo and in vivo cardiac electrophysiological effects

Pilote

Simard

Drolet

2022

Journal of Cardiovascular Pharmacology

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Bradycardia and QTc interval prolongation on the ECG have been reported with remdesivir (Veklury), an antiviral drug recently approved for treating severely ill patients with COVID-19. The objective was to evaluate the effects of remdesivir on cardiac electrophysiology ex vivo and in vivo. Ex vivo: Langendorff retroperfusion experiments were performed on isolated hearts from male Hartley guinea pigs (n = 23, total) exposed to either remdesivir 3, 10, or 30 mmol/L to assess drug-induced prolongation of the monophasic action potential duration measured at 90% repolarization (MAPD 90 ). In vivo: ECG recordings using wireless cardiac telemetry were performed in guinea pigs (n = 6) treated with daily i.p. doses of remdesivir 5 mg/kg on day 1 and 2.5 mg/kg on days 2-10. Ex vivo remdesivir (3, 10, and 30 mmol/L) had no statistically significant effect on MAPD 90 , while pacing the hearts at basic stimulation cycle lengths of 200 or 250 milliseconds, or when the hearts were not paced and beating at their intrinsic heart rate. In a second set of similar ex vivo experiments, remdesivir 10 mmol/L did not potentiate the MAPD 90 -prolonging effects of dofetilide 20 nmol/L (n = 4) hearts. In vivo remdesivir caused small but statistically significant prolongations of the RR and QTc F intervals at day 1 (5 mg/kg) and at day 10 (2.5 mg/kg). No ventricular arrhythmias were ever observed under the effect of remdesivir. Remdesivir causes bradycardia, and mild QTc prolongation, which nonetheless, could be of clinical relevance in many hospitalized patients with COVID-19 concomitantly treated with multiple drugs.

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Iloperidone (Fanapt®), a novel atypical antipsychotic, is a potent HERG blocker and delays cardiac ventricular repolarization at clinically relevant concentration

Cited by 13 publications

References 20 publications

A case of iloperidone overdose in a 27-year-old man with cocaine abuse

A case of iloperidone overdose in a 27-year-old man with cocaine abuse

Ventricular premature contractions associated with iloperidone

Remdesivir (VEKLURY) for treating COVID-19: Guinea pig ex vivo and in vivo cardiac electrophysiological effects

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