Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat |
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Authors: | Meng Harry Cao James Kang Jiesheng Ying Xiaoyou Ji Junzhi Reynolds William Rampe David |
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Affiliation: | Disposition, Safety, and Animal Research, sanofi-aventis US Inc., Route 202-206, Bridgewater, NJ 08807, USA |
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Abstract: | Mephedrone (4-methylmethcathinone) is a new and popular drug of abuse widely available on the Internet and still legal in some parts of the world. Clinical reports are now emerging suggesting that the drug displays sympathomimetic toxicity on the cardiovascular system but no studies have yet explored its cardiovascular effects. Therefore we examined the effects of mephedrone on the cardiovascular system using a combination of in vitro electrophysiology and in vivo hemodynamic and echocardiographic measurements. Patch clamp studies revealed that mephedrone, up to 30 μM, had little effect on the major voltage-dependent ion channels of the heart or on action potentials recorded in guinea pig myocytes. Subcutaneous administration of mephedrone (3 and 15 mg/kg) to conscious telemetry-implanted rats produced dose-dependent increases in heart rate and blood pressure which persisted after pre-treatment with reserpine. Echocardiographic analysis demonstrated that intravenous injection of mephedrone (0.3 and 1 mg/kg) increased cardiac function, including cardiac output, ejection fraction, and stroke volume, similar to methamphetamine (0.3 mg/kg). We conclude that mephedrone is not directly pro-arrhythmic, but induces substantial increases in heart rate, blood pressure and cardiac contractility and this activity contributes to the cardiovascular toxicity in people who abuse the drug. |
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Keywords: | CHO, Chinese hamster ovary HERG, human ether-a-go-go-related gene ANOVA, analysis of variance ECG, electrocardiogram LVIDD, left ventricular internal diameter in diastole LVIDS, left ventricular internal diameter in systole LVVD, left ventricular volume in diastole LVVS, left ventricular volume in systole |
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