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High affinity blockade of the HERG cardiac K(+) channel by the neuroleptic pimozide.
Eur J Pharmacol. 2000 Mar 31; 392(3):137-40.EJ

Abstract

Pimozide is an antipsychotic agent also used to treat facial tics. Pimozide can cause acquired long QT syndrome and ventricular arrhythmias. To elucidate the mechanism behind these clinical findings, we examined the effects of pimozide on the cloned human cardiac K(+) channels HERG (human ether-a-go-go-related gene; rapid component of delayed rectifier), Kv1.5 (ultra-rapid delayed rectifier) and KvLQT1/minK (slow component of delayed rectifier). Using patch clamp electrophysiology, we found that pimozide was a potent inhibitor of HERG displaying an IC(50) value of 18 nM. In contrast, pimozide (10 microM) was a weak inhibitor of KvLQT1/minK and Kv1.5. We conclude that pimozide is a specific, high affinity antagonist of HERG, and that this interaction leads to prolongation of cardiac repolarization.

Authors+Show Affiliations

Aventis Pharmaceuticals, Route 202-206, P.O. Box 6800, Bridgewater, NJ 08807-0800, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10762666

Citation

Kang, J, et al. "High Affinity Blockade of the HERG Cardiac K(+) Channel By the Neuroleptic Pimozide." European Journal of Pharmacology, vol. 392, no. 3, 2000, pp. 137-40.
Kang J, Wang L, Cai F, et al. High affinity blockade of the HERG cardiac K(+) channel by the neuroleptic pimozide. Eur J Pharmacol. 2000;392(3):137-40.
Kang, J., Wang, L., Cai, F., & Rampe, D. (2000). High affinity blockade of the HERG cardiac K(+) channel by the neuroleptic pimozide. European Journal of Pharmacology, 392(3), 137-40.
Kang J, et al. High Affinity Blockade of the HERG Cardiac K(+) Channel By the Neuroleptic Pimozide. Eur J Pharmacol. 2000 Mar 31;392(3):137-40. PubMed PMID: 10762666.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High affinity blockade of the HERG cardiac K(+) channel by the neuroleptic pimozide. AU - Kang,J, AU - Wang,L, AU - Cai,F, AU - Rampe,D, PY - 2000/4/14/pubmed PY - 2000/5/20/medline PY - 2000/4/14/entrez SP - 137 EP - 40 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 392 IS - 3 N2 - Pimozide is an antipsychotic agent also used to treat facial tics. Pimozide can cause acquired long QT syndrome and ventricular arrhythmias. To elucidate the mechanism behind these clinical findings, we examined the effects of pimozide on the cloned human cardiac K(+) channels HERG (human ether-a-go-go-related gene; rapid component of delayed rectifier), Kv1.5 (ultra-rapid delayed rectifier) and KvLQT1/minK (slow component of delayed rectifier). Using patch clamp electrophysiology, we found that pimozide was a potent inhibitor of HERG displaying an IC(50) value of 18 nM. In contrast, pimozide (10 microM) was a weak inhibitor of KvLQT1/minK and Kv1.5. We conclude that pimozide is a specific, high affinity antagonist of HERG, and that this interaction leads to prolongation of cardiac repolarization. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/10762666/High_affinity_blockade_of_the_HERG_cardiac_K_+__channel_by_the_neuroleptic_pimozide_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014299900001230 DB - PRIME DP - Unbound Medicine ER -