Serotonin-4 receptor antagonists reverse cocaine-induced cardiac arrhythmia.
The effect of the 5-HT4 antagonists GR113808A and GR125487D on cocaine-induced cardiac arrhythmia was examined in the rat. Cocaine alone, given i.v. at a rate of 2 mg/kg every 5 min, produced an initial increase in blood pressure followed by a severe drop in pressure and bradycardia. Sustained ventricular fibrillation was noted after 6-12 mg/kg cocaine and quickly progressed to asystole. Pretreatment with both GR113808A and GR125487D antagonized these effects in a dose-dependent manner. When given after the onset of arrhythmia, both drugs reversed the cocaine-induced arrhythmia's. Thus, the 5-HT4 antagonists may be useful in the treatment of cocaine toxicity.
Ohuoha
D C
DC
Clinical Psychopharmacology Section, NIH/NIDA/IRP, Baltimore, MD 21224, USA.
Schindler
C W
CW
Rothman
R B
RB
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014662:Vasoconstrictor Agents; D044422:Receptors, Serotonin, 5-HT4; D003042:Cocaine