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

1 Studies were designed to examine the effects of alpha(1) (alpha(1)AR)-plus beta3-adrenoreceptor (beta(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. 2 MDMA (40 mg kg(-1), s.c.) induced a rapid and robust increase in rectal temperature, which was significantly attenuated by pretreatment with the alpha(1)AR antagonist prazosin (100 mug kg(-1), i.p.) plus the beta(3)AR antagonist SR59230A (5 mg kg(-1), i.p.). 3 CK levels significantly increased ( peaking at 4 h) after MDMA treatment and were blocked by the combination of prazosin plus SR59230A. 4 At 4 h after MDMA treatment, BUN and sCr levels were also significantly increased and could be prevented by this combination of alpha(1)AR-plus beta(3)AR-antagonists. 5 The results from this study suggest that alpha(1)AR and beta(3)AR play a critical role in the etiology of MDMA-mediated hyperthermia and subsequent rhabdomyolysis. British Journal of Pharmacology (2004).