Effects of MDMA, MDA and MDEA on blood pressure, heart rate, locomotor activity and body temperature in the rat involveα‐adrenoceptors

In conscious rats, the amphetamine derivatives MDMA, MDA, and MDEA (each at 20 mg/kg) affected blood pressure, heart rate, body temperature, and movement. MDA caused the largest and most prolonged rise in blood pressure, accompanied by a slowed heart rate, while MDEA produced a brief, non-significant drop in diastolic pressure. All three initially lowered core body temperature, but MDA later caused a rise in temperature, with recovery speed fastest for MDA, then MDMA, then MDEA. Blocking α2A-adrenoceptors with BRL 44408 prolonged MDMA's hypothermic effect and triggered increased movement only with MDMA. In isolated rat aorta and vas deferens, the drugs' potency for contraction matched MDA > MDMA > MDEA, with MDEA acting as an antagonist.

Study at a glance

Abstract

The effects of injection of 3,4‐methylenedioxymethamphetamine (MDMA), 3,4‐methylenedioxyamphetamine (MDA) and N ‐ethyl‐3,4‐methylenedioxyamphetamine (MDEA) (all 20 mg kg −1 ) on blood pressure, heart rate, core body temperature and locomotor activity in conscious rats were investigated using radiotelemetry. MDMA and MDA produced a prolonged increase in both systolic and diastolic pressures, with MDA causing the most marked rise. MDEA produced a transient but nonsignificant fall in diastolic pressure. The pressor response produced by MDA was accompanied by bradycardia. All three amphetamine derivatives caused an initial hypothermic response; however, MDA also produced a subsequent hyperthermia, and the speed of recovery from hypothermia was MDA>MDMA>MDEA. The α 2A ‐adrenoceptor antagonist 2‐((4,5‐dihydro‐1 H ‐imidazol‐2‐yl)methyl)‐2,3‐dihydro‐1‐methyl‐1 H ‐isoindole (BRL 44408) (1 mg kg −1 ) prolonged the hypothermic response to MDMA. Only MDA induced locomotor activity when given alone, but in the presence of BRL 44408, MDMA produced increased locomotor activity. The order of potency for producing isometric contractions of rat aorta ( α 1D ) and vas deferens ( α 1A ) was MDA>MDMA>MDEA, with MDEA acting as an α 1 ‐adrenoceptor antagonist with a p K B of 4.79±0.12 ( n =4) in aorta. The order of potency for prejunctional inhibition of stimulation‐evoked contractions in rat vas deferens ( α 2A ‐adrenoceptor mediated) was MDA>MDMA>MDEA. Blood pressure actions of the three amphetamine derivatives may be at least partly due to α 1 ‐adrenoceptor agonism or antagonism. The reversal of the hypothermic actions are at least partly due to α 2A ‐adrenoceptor agonism since the hypothermic response was more prolonged with MDEA which exhibits low α 2A ‐adrenoceptor potency, and effects of MDMA after α 2A ‐adrenoceptor antagonism were similar to those of MDEA. British Journal of Pharmacology (2006) 147 , 926–934. doi: 10.1038/sj.bjp.0706688