Attenuation of 3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy)‐induced rhabdomyolysis with α1‐ plus β3‐adrenoreceptor antagonists

In male rats, the drug MDMA (Ecstasy) caused a rapid and large increase in body temperature, which was significantly reduced by blocking two types of receptors: α₁-adrenoreceptors and β₃-adrenoreceptors. MDMA also raised levels of creatine kinase (a marker of muscle breakdown, peaking at 4 hours) and increased blood urea nitrogen and serum creatinine (markers of kidney function) at 4 hours. These effects were prevented by giving a combination of the α₁ antagonist prazosin and the β₃ antagonist SR59230A. The findings indicate that both receptor types are critically involved in MDMA-induced hyperthermia and the resulting muscle damage.

Study at a glance

Abstract

Studies were designed to examine the effects of α 1 ( α 1 AR)‐ plus β 3 ‐adrenoreceptor ( β 3 AR) antagonists on 3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy)‐induced hyperthermia and measures of rhabdomyolysis (creatine kinase (CK)) and renal function (blood urea nitrogen (BUN) and serum creatinine (sCr)) in male Sprague–Dawley rats. MDMA (40 mg kg −1 , s.c.) induced a rapid and robust increase in rectal temperature, which was significantly attenuated by pretreatment with the α 1 AR antagonist prazosin (100 μ g kg −1 , i.p.) plus the β 3 AR antagonist SR59230A (5 mg kg −1 , i.p.). CK levels significantly increased (peaking at 4 h) after MDMA treatment and were blocked by the combination of prazosin plus SR59230A. At 4 h after MDMA treatment, BUN and sCr levels were also significantly increased and could be prevented by this combination of α 1 AR‐ plus β 3 AR‐antagonists. The results from this study suggest that α 1 AR and β 3 AR play a critical role in the etiology of MDMA‐mediated hyperthermia and subsequent rhabdomyolysis. British Journal of Pharmacology (2004) 142 , 667–670. doi: 10.1038/sj.bjp.0705823