Cardiovascular and sympathetic responses and reflex changes elicited by MDMA.
The recreational use of 3,4-methylenedioxymethamphetamine (MDMA) has increased as have the number of clinical reports linking MDMA use with cardiovascular toxicity. Nonetheless, the cardiovascular and sympathetic nerve responses elicited by MDMA have not been well characterized. The purpose of this study was to characterize the mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve responses elicited by the acute administration of MDMA and to determine whether neurotoxic doses of MDMA change cardiovascular and/or cardiovascular reflex function. In conscious rats, MDMA or d-amphetamine elicited similar dose-dependent increases in MAP. MDMA elicited significant bradycardia at doses above 1.0 mg/kg. Pretreatment with phentolamine significantly reduced the duration but not the magnitude of the pressor response elicited by MDMA. In pentobarbital-anesthetized rats, MDMA (0.1 mg/kg) increased renal sympathetic nerve activity (RSNA; 33 +/- 10%), while larger doses significantly decreased RSNA (-91 +/- 3%, max). Neurotoxic doses of MDMA (20 mg/kg, s.c., b.i.d. for 4 days) significantly enhanced the bradycardic component of the Bezold-Jarisch reflex elicited by i.v. serotonin when tested either 2 days or 2 weeks after the last neurotoxic treatment. However, neurotoxic treatment did not significantly affect baroreceptor reflex function. These results indicate that the acute administration of MDMA and d-amphetamine produce similar cardiovascular and sympathetic responses. Neurotoxic doses of MDMA can also significantly alter cardiovascular reflex function. These findings raise the possibility that MDMA may have the potential to produce cardiovascular and/or cardiac toxicity similar to that elicited by other amphetamine analogs.
O'Cain
P A
PA
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, 1901 Perdido St., New Orleans, LA 70112, USA.
Hletko
S B
SB
Ogden
B A
BA
Varner
K J
KJ
D000661:Amphetamine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology* / Q000633:toxicity; D013564:Sympathetic Nervous System / Q000187:drug effects*
D018765:Dopamine Uptake Inhibitors; D018490:Serotonin Agents; D012701:Serotonin; D000661:Amphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine