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

1 The effects of injection of 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy-amphetamine (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. 2 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. 3 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 alpha(2A)-adrenoceptor antagonist 2-((4,5-dihydro-1H-imidazol-2-yl)methyl)-2,3-dihydro- 1-methyl-1H-isoindole (BRL 44408) (1 mg kg(-1)) prolonged the hypothermic response to MDMA. 4 Only MDA induced locomotor activity when given alone, but in the presence of BRL 44408, MDMA produced increased locomotor activity. 5 The order of potency for producing isometric contractions of rat aorta (alpha(1D)) and vas deferens (alpha(1A)) was MDA > MDMA > MDEA, with MDEA acting as an alpha(1)-adrenoceptor antagonist with a pK(B) of 4.79 +/- 0.12 (n = 4) in aorta. 6 The order of potency for prejunctional inhibition of stimulation-evoked contractions in rat vas deferens (alpha(2A)-adrenoceptor mediated) was MDA > MDMA > MDEA. 7 Blood pressure actions of the three amphetamine derivatives may be at least partly due to alpha(1)-adrenoceptor agonism or antagonism. The reversal of the hypothermic actions are at least partly due to alpha(2A)-adrenoceptor agonism since the hypothermic response was more prolonged with MDEA which exhibits low alpha(2A)-adrenoceptor potency, and effects of MDMA after alpha(2A)-adrenoceptor antagonism were similar to those of MDEA.