![]() |
|
|
Vol. 302, Issue 3, 898-907, September 2002
Department of Pharmacology and Experimental Therapeutics, Louisiana
State University Health Sciences Center (A.H., K.L., B.A.O., K.J.V.);
Loyola University New Orleans (L.A.B.); and Department of Pathology,
Tulane School of Medicine, New Orleans, Louisiana (S.M.-S.)
The recreational use of 3,4-methylenedioxymethamphetamine (MDMA;
Ecstasy) is often characterized by a repeated pattern of frequent drug
administrations (binge) followed by a period of abstinence.
Radiotelemetry was used to characterize the cardiovascular responses
elicited during three MDMA binges (3 or 9 mg/kg b.i.d. for 4 days),
each of which was separated by a 10-day MDMA-free period. The heart
rate and mean arterial pressure (MAP) responses elicited by 3-mg/kg
doses of MDMA were consistent within and between the three binges. In
the first binge the 9-mg/kg doses of MDMA increased MAP and produced a
biphasic (decrease/increase) heart rate response. The bradycardia
elicited by MDMA in the first binge (
75 bpm) was enhanced in the
second and third binges (
186 and
287 bpm, respectively).
Significant hypotension accompanied the increased bradycardic
responses. Atropine abolished the hypotension and significantly
attenuated the bradycardic responses. The MAP and heart rate responses
elicited by sodium nitroprusside, acetylcholine, phenylephrine, and
serotonin (5-HT) were evaluated before each binge and 10 days after the
last binge. The hypotension, but not the tachycardia elicited by sodium
nitroprusside was attenuated by the repeated administration of MDMA.
The responses to phenylephrine, acetylcholine, and 5-HT were unaltered
after MDMA. The hearts of treated rats contained foci of inflammatory
infiltrates (lymphocytes and macrophages), some of which contained
necrotic cells and/or disrupted cytoarchitecture. MDMA produced cardiac
arrhythmias in some rats. These results indicate that the binge
administration of MDMA can significantly alter cardiovascular and
cardiovascular reflex function and produce cardiac toxicity.