[Arrhythmogenic effects of sultopride chlorhydrate: clinical and cellular electrophysiological correlation].
This study was designed following the first documented case of torsades de pointes induced by sultopride hydrochloride, a substituted benzamide neuroleptic drug. The patient, a 48 year-old woman with no known cardiovascular disease, had been treated for several years with this drug. She was admitted for severe bronchospasm requiring artificial ventilation. Twenty-one hours after her admission, she developed several episodes of torsades de pointes, which were successfully treated with magnesium sulphate. At that time, the QT interval was 500 ms for a heart rate of 108 b.min-1 (QTc of 668 ms, and theoretical QTc 370 ms). On the fourth day, QTc was 548 ms and theoretical QTc 370 ms. The sultopride was stopped on the fifth day. Two days later, QTc was 397 ms. Six months later, there was no recurrence. Several cases of TdP or sudden death have been reported in patients receiving neuroleptic drugs. The effects of sultopride hydrochloride were therefore tested on isolated ferret Purkinje fibres, using the microelectrode technique. Three concentrations of the drug (D1, D2, D3) were tested, as well as normal Tyrode solution. Maximum diastolic potentials (Vmax) were -88.37 +/- 0.89 mV (control), -89.08 +/- 1.20 mV (D1), -90.00 +/- 1.06 mV (D2), and -90.14 +/- 1.20 mV (D3). Vmax was not affected by sultopride during pacing at 1,000 ms of cycle length. The duration of the action potential increased with the drug concentration. There was no early after-depolarisation (EAD) during control, and 7 out of 9 fibers had EAD and 3 out of 9 triggered activity in D3. The solvent (benzyl alcohol) did not modify the action potential.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinique cardiologique, Hôpital G et R Laënnec, Nantes.
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G
Lande
E
E
Drouin
C
C
Gauthier
J C
JC
Chevallier
J F
JF
Godin
A
A
Chiffoleau
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H
Le Marec
D000200:Action Potentials / Q000187:drug effects; D000077582:Amisulpride; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008278:Magnesium Sulfate / Q000627:therapeutic use; D008875:Middle Aged; D011690:Purkinje Fibers / Q000187:drug effects; D012107:Research Design; D013469:Sulpiride / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D016171:Torsades de Pointes / Q000139:chemically induced* / Q000188:drug therapy
D014150:Antipsychotic Agents; D008278:Magnesium Sulfate; D013469:Sulpiride; D000077582:Amisulpride
Effets arythmogènes du chlorydrate de sultopride: corrélation clinique et électrophysiologique cellulaire.