Abstract
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.
MeSH terms
-
Adrenergic alpha-1 Receptor Antagonists
-
Adrenergic beta-3 Receptor Antagonists
-
Animals
-
Blood Urea Nitrogen
-
Body Temperature / drug effects
-
Body Temperature / physiology
-
Creatine Kinase / antagonists & inhibitors
-
Creatine Kinase / blood
-
Drug Administration Schedule
-
Drug Therapy, Combination
-
Fever / chemically induced
-
Fever / physiopathology
-
Injections, Intraperitoneal
-
Injections, Subcutaneous
-
Male
-
N-Methyl-3,4-methylenedioxyamphetamine / administration & dosage
-
N-Methyl-3,4-methylenedioxyamphetamine / adverse effects*
-
N-Methyl-3,4-methylenedioxyamphetamine / antagonists & inhibitors
-
Prazosin / administration & dosage
-
Prazosin / blood
-
Prazosin / pharmacokinetics
-
Propanolamines / administration & dosage
-
Propanolamines / blood
-
Propanolamines / pharmacokinetics
-
Rats
-
Rats, Sprague-Dawley
-
Receptors, Adrenergic, alpha-1 / administration & dosage
-
Receptors, Adrenergic, alpha-1 / therapeutic use*
-
Receptors, Adrenergic, beta-3 / administration & dosage
-
Receptors, Adrenergic, beta-3 / therapeutic use*
-
Rhabdomyolysis / chemically induced*
-
Rhabdomyolysis / prevention & control*
-
Time Factors
Substances
-
3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate
-
Adrenergic alpha-1 Receptor Antagonists
-
Adrenergic beta-3 Receptor Antagonists
-
Propanolamines
-
Receptors, Adrenergic, alpha-1
-
Receptors, Adrenergic, beta-3
-
Creatine Kinase
-
N-Methyl-3,4-methylenedioxyamphetamine
-
Prazosin