Attenuation of 3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy)‐induced rhabdomyolysis with α1‐ plus β3‐adrenoreceptor antagonists
Jon E. Sprague, Robert E. Brutcher, Edward Mills, David Caden, Daniel E. Rusyniak
British Journal of Pharmacology June 1, 2004 DOI: 10.1038/sj.bjp.0705823 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Male Sprague–Dawley rats |
| Interventions | MDMA Prazosin SR59230A |
| Dose | MDMA 40 mg kg−1 s.c.; prazosin 100 μg kg−1 i.p.; SR59230A 5 mg kg−1 i.p. |
| Duration | 4 hours post-MDMA |
| Measures | rectal temperature, creatine kinase (CK), blood urea nitrogen (BUN), serum creatinine (sCr) |
| Topics | MDMA |
| Keywords | Rhabdomyolysis Prazosin Antagonist Pharmacology Hyperthermia Blood urea nitrogen Creatine kinase Endocrinology Creatinine |
| Citations | 53 |
| Key findings | Blocking α₁- and β₃-adrenoreceptors together prevented MDMA-induced hyperthermia and markers of rhabdomyolysis and kidney impairment in rats. |
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