Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat.
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 1mg/kg) increased cardiac function, including cardiac output, ejection fraction, and stroke volume, similar to methamphetamine (0.3mg/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.
Disposition, Safety, and Animal Research, sanofi-aventis US Inc., Route 202-206, Bridgewater, NJ 08807, USA. harry.meng@sanofi.com
Harry
H
Meng
James
J
Cao
Jiesheng
J
Kang
Xiaoyou
X
Ying
Junzhi
J
Ji
William
W
Reynolds
David
D
Rampe
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D015198:Designer Drugs / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D022062:Electrophysiologic Techniques, Cardiac; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced; D013287:Illicit Drugs / Q000633:toxicity*; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000633:toxicity; D032383:Myocytes, Cardiac / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013610:Tachycardia / Q000139:chemically induced; D023382:Toxicity Tests, Acute
D015198:Designer Drugs; D013287:Illicit Drugs; D008694:Methamphetamine; C548233:mephedrone