MeDieViL
Bluelighter
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- Feb 11, 2007
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It has been shown to reverse mdma induced hyperthermia, serotonin increases body temperature trough the 5ht2a receptor, so therefor my question.
Or is this purely related to its cardiocalming effects?
Carvedilol reverses hyperthermia and attenuates rhabdomyolysis induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in an animal model.
Sprague JE1, Moze P, Caden D, Rusyniak DE, Holmes C, Goldstein DS, Mills EM.
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Abstract
OBJECTIVE:
Hyperthermia is a potentially fatal manifestation of severe 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) intoxication. No proven effective drug treatment exists to reverse this potentially life-threatening hyperthermia, likely because mechanisms of peripheral thermogenesis are poorly understood. Using a rat model of MDMA hyperthermia, we evaluated the acute drug-induced changes in plasma catecholamines and used these results as a basis for the selection of drugs that could potentially reverse this hyperthermia.
DESIGN:
Prospective, controlled, randomized animal study.
SETTING:
A research institute laboratory.
SUBJECTS:
Male, adult Sprague-Dawley rats.
INTERVENTIONS:
Based on MDMA-induced changes in plasma catecholamine levels, rats were subjected to the nonselective (beta1 + beta2) adrenergic receptor antagonists propranolol or nadolol or the alpha1- + beta1,2,3-adrenergic receptor antagonist carvedilol before or after a thermogenic challenge of MDMA.
MEASUREMENT AND MAIN RESULTS:
Plasma catecholamines levels 30 mins after MDMA (40 mg/kg, subcutaneously) were determined by high-pressure liquid chromatography and electrochemical detection. Core temperature was measured by a rectal probe attached to a thermocouple. Four hours after MDMA treatment, blood was drawn and serum creatine kinase levels were measured as a marker of rhabdomyolysis using a Vitros analyzer. MDMA induced a 35-fold increase in norepinephrine levels, a 20-fold increase in epinephrine, and a 2.4-fold increase in dopamine levels. Propranolol (10 mg/kg, intraperitoneally) or nadolol (10 mg/kg, intraperitoneally) administered 30 mins before MDMA had no effect on the thermogenic response. In contrast, carvedilol (5 mg/kg, intraperitoneally) administered 15 mins before or after MDMA prevented this hyperthermic response. Moreover, when administered 1 hr after MDMA, carvedilol completely reversed established hyperthermia and significantly attenuated subsequent MDMA-induced creatine kinase release.
CONCLUSION:
These data show that alpha1 and beta3-adrenergic receptors may contribute to the mediation of MDMA-induced hyperthermia and that drugs targeting these receptors, such as carvedilol, warrant further investigation as novel therapies for the treatment of psychostimulant-induced hyperthermia and its sequelae.
Or is this purely related to its cardiocalming effects?
Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans
CM Hysek,1 Y Schmid,1 A Rickli,1 LD Simmler,1 M Donzelli,1 E Grouzmann,2 and ME Liechti1
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Abstract
BACKGROUND AND PURPOSE
The use of ±3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is associated with cardiovascular complications and hyperthermia.
EXPERIMENTAL APPROACH
We assessed the effects of the α1- and β-adrenoceptor antagonist carvedilol on the cardiostimulant, thermogenic and subjective responses to MDMA in 16 healthy subjects. Carvedilol (50 mg) or placebo was administered 1 h before MDMA (125 mg) or placebo using a randomized, double-blind, placebo-controlled, four-period crossover design.
KEY RESULTS
Carvedilol reduced MDMA-induced elevations in blood pressure, heart rate and body temperature. Carvedilol did not affect the subjective effects of MDMA including MDMA-induced good drug effects, drug high, drug liking, stimulation or adverse effects. Carvedilol did not alter the plasma exposure to MDMA.
CONCLUSIONS AND IMPLICATIONS
α1- and β-Adrenoceptors contribute to the cardiostimulant and thermogenic effects of MDMA in humans but not to its psychotropic effects. Carvedilol could be useful in the treatment of cardiovascular and hyperthermic complications associated with ecstasy use.
No acces to full textToward directed therapy for amphetamine-mediated hyperthermia: is carvedilol worth raving about?