Effects of MDMA, MDA and MDEA on blood pressure, heart rate, locomotor activity and body temperature in the rat involve alpha-adrenoceptors
by
Bexis S, Docherty JR.
1Department of Physiology,
Royal College of Surgeons in Ireland,
123 St Stephen's Green, Dublin 2, Ireland.
Br J Pharmacol. 2006 Feb 20;

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 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.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 (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.The order of potency for prejunctional inhibition of stimulation-evoked contractions in rat vas deferens (alpha(2A)-adrenoceptor mediated) was MDA>MDMA>MDEA.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

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