Attenuation of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-induced rhabdomyolysis with alpha1- plus beta3-adrenoreceptor antagonists.
1. Studies were designed to examine the effects of alpha(1) (alpha(1)AR)- plus beta(3)-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 x 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 microg x kg(-1), i.p.) plus the beta(3)AR antagonist SR59230A (5 mg x 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.
Sprague
Jon E
JE
The Department of Pharmaceutical and Biomedical Sciences, The Raabe College of Pharmacy, Ohio Northern University, Ada, OH 45810, USA. j-sprague@onu.edu
Brutcher
Robert E
RE
Mills
Edward M
EM
Caden
David
D
Rusyniak
Daniel E
DE
D058668:Adrenergic alpha-1 Receptor Antagonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000818:Animals; D001806:Blood Urea Nitrogen; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D003402:Creatine Kinase / Q000037:antagonists & inhibitors / Q000097:blood; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D011224:Prazosin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011412:Propanolamines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000008:administration & dosage / Q000627:therapeutic use*; D022702:Receptors, Adrenergic, beta-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D012206:Rhabdomyolysis / Q000139:chemically induced* / Q000517:prevention & control*; D013997:Time Factors
C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D058668:Adrenergic alpha-1 Receptor Antagonists; D058673:Adrenergic beta-3 Receptor Antagonists; D011412:Propanolamines; D018340:Receptors, Adrenergic, alpha-1; D022702:Receptors, Adrenergic, beta-3; D003402:Creatine Kinase; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D011224:Prazosin