Attenuation of 3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy)‐induced rhabdomyolysis with α1‐ plus β3‐adrenoreceptor antagonists
British Journal of Pharmacology – June 01, 2004
Source: OpenAlex
Summary
MDMA, commonly known as Ecstasy, significantly raises body temperature in male Sprague-Dawley rats, with a notable 40 mg/kg dose causing hyperthermia. However, pretreatment with prazosin and SR59230A effectively reduced this temperature spike. Additionally, MDMA treatment led to a marked increase in creatine kinase levels, peaking at four hours, alongside elevated blood urea nitrogen and serum creatinine, indicating potential kidney stress. The combination of these antagonists successfully mitigated both hyperthermia and rhabdomyolysis effects, highlighting their critical role in managing MDMA's toxic consequences.
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