Cardiovascular Changes Induced By Drugs of Abuse

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Research over the past year has focused on the cardiovascular effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its metabolites (MDA, HHMA, HMMA, HMA, HHA) in rats. N-Demethylation of MDMA gives rise to 3,4-methylenedioxyamphetamine (MDA). O-Demethylaiton of MDMA and MDA gives rise to 3,4-dihyroxymethamphetamine (HHMA) and 3,4-dihydroxyamphetamine (HHA). HHMA and HHA are O-methylated to form 4-hyroxy-3-methoxymethamhetamine (HMMA) and 4-hydroxy-3-methoxyamphetamine (HMA). Rats were implanted with telemetry transmitters with the catheter in the descending aorta. These devices allow for the measurement of blood pressure, heart rate and locomotor activity in freely moving rats. MDMA and the metabolites were then administered i.p. and cardiovascular parameters were measured for 2 hours. Preliminary data suggest that MDMA increases locomotor activity and produces moderate increases in blood pressure and heart rate. MDA has effects very similar to MDMA. In contrast, the metabolite HHMA increases activity and heart rate, but has no effect on blood pressure. The metabolite HMMA decreases activity and has no effect on BP or HR. We do not have enough data for HMMA and HMA to make any conclusions. These results suggest that the metabolites of MDMA may contribute to its overall cardiovascular effects in ways that do not mimic the parent compound.