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Comparison of the effects of methadone and heroin on human ether-à-go-go-related gene channels.
Cardiovasc Toxicol. 2010 Sep; 10(3):161-5.CT

Abstract

Torsades de pointes (TdP) is a life-threatening form of ventricular arrhythmia that occurs under conditions of delayed cardiac repolarization indicated by prolonged QT intervals in ECG recordings. The main mechanism of QT prolongation and TdP is block of the rapid component of the cardiac delayed rectifier K(+) current (I(Kr)), which is encoded by hERG (human ether-à-go-go-related gene). The opioid agonist methadone has previously been demonstrated to inhibit hERG currents, and there are reports of serious cardiac arrhythmias and deaths from TdP and ventricular fibrillation in patients taking methadone. The aim of the present study was to compare the effects of the opioid agonists methadone and heroin (3,6-diacetylmorphine) on hERG currents stably expressed in human embryonic kidney (HEK 293) cells using the whole-cell configuration of the patch-clamp technique. Both methadone and heroin inhibit hERG currents in a concentration-dependent manner. The following values were calculated for IC(50) (concentration causing half-maximal inhibition) and n (the Hill coefficient): 4.8 microM and 0.9 for methadone, 427 microM and 0.7 for heroin. In conclusion, the potency for block of hERG currents is about 100-fold lower for heroin when compared to methadone.

Authors+Show Affiliations

Federal Institute for Drugs and Medical Devices, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany. Jochen.Zuenkler@bfarm.deNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

20467834

Citation

Zünkler, Bernd J., and Maria Wos-Maganga. "Comparison of the Effects of Methadone and Heroin On Human Ether-à-go-go-related Gene Channels." Cardiovascular Toxicology, vol. 10, no. 3, 2010, pp. 161-5.
Zünkler BJ, Wos-Maganga M. Comparison of the effects of methadone and heroin on human ether-à-go-go-related gene channels. Cardiovasc Toxicol. 2010;10(3):161-5.
Zünkler, B. J., & Wos-Maganga, M. (2010). Comparison of the effects of methadone and heroin on human ether-à-go-go-related gene channels. Cardiovascular Toxicology, 10(3), 161-5. https://doi.org/10.1007/s12012-010-9074-y
Zünkler BJ, Wos-Maganga M. Comparison of the Effects of Methadone and Heroin On Human Ether-à-go-go-related Gene Channels. Cardiovasc Toxicol. 2010;10(3):161-5. PubMed PMID: 20467834.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of the effects of methadone and heroin on human ether-à-go-go-related gene channels. AU - Zünkler,Bernd J, AU - Wos-Maganga,Maria, PY - 2010/5/15/entrez PY - 2010/5/15/pubmed PY - 2010/12/14/medline SP - 161 EP - 5 JF - Cardiovascular toxicology JO - Cardiovasc. Toxicol. VL - 10 IS - 3 N2 - Torsades de pointes (TdP) is a life-threatening form of ventricular arrhythmia that occurs under conditions of delayed cardiac repolarization indicated by prolonged QT intervals in ECG recordings. The main mechanism of QT prolongation and TdP is block of the rapid component of the cardiac delayed rectifier K(+) current (I(Kr)), which is encoded by hERG (human ether-à-go-go-related gene). The opioid agonist methadone has previously been demonstrated to inhibit hERG currents, and there are reports of serious cardiac arrhythmias and deaths from TdP and ventricular fibrillation in patients taking methadone. The aim of the present study was to compare the effects of the opioid agonists methadone and heroin (3,6-diacetylmorphine) on hERG currents stably expressed in human embryonic kidney (HEK 293) cells using the whole-cell configuration of the patch-clamp technique. Both methadone and heroin inhibit hERG currents in a concentration-dependent manner. The following values were calculated for IC(50) (concentration causing half-maximal inhibition) and n (the Hill coefficient): 4.8 microM and 0.9 for methadone, 427 microM and 0.7 for heroin. In conclusion, the potency for block of hERG currents is about 100-fold lower for heroin when compared to methadone. SN - 1559-0259 UR - https://www.unboundmedicine.com/medline/citation/20467834/Comparison_of_the_effects_of_methadone_and_heroin_on_human_ether_à_go_go_related_gene_channels_ L2 - https://dx.doi.org/10.1007/s12012-010-9074-y DB - PRIME DP - Unbound Medicine ER -