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Methadone remains the cornerstone of treatment for narcotic dependence. Like many psychotropic medications, methadone is a racemic mixture of R- and S-isomers. Researchers in Switzerland investigated whether one or both enantiomers are responsible for torsades de pointes and sudden deaths recently reported in patients receiving high doses of methadone.
In isolated cardiac cells, S-methadone was 62% more potent than R-methadone in blocking the hERG potassium channel, which repolarizes cardiac cells. Of 179 patients receiving methadone maintenance, 9% had a prolonged QTc interval, and 26% had a borderline QTc interval. QTc interval correlated weakly with methadone dose and more strongly with plasma levels. Patients with methadone levels above …