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

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 alpha2A-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 (alpha1D) and vas deferens (alpha1A) was MDA>MDMA>MDEA, with MDEA acting as an alpha1-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 (alpha2A-adrenoceptor mediated) was MDA>MDMA>MDEA. Blood pressure actions of the three amphetamine derivatives may be at least partly due to alpha1-adrenoceptor agonism or antagonism. The reversal of the hypothermic actions are at least partly due to alpha2A-adrenoceptor agonism since the hypothermic response was more prolonged with MDEA which exhibits low alpha2A-adrenoceptor potency, and effects of MDMA after alpha2A-adrenoceptor antagonism were similar to those of MDEA.

Figure 1

(a) Mean blood pressure and (b) heart rate recordings in conscious rats before and after the administration of vehicle, MDMA (20 mg kg⁻¹), MDA (20 mg kg⁻¹) or MDEA (20 mg kg⁻¹) at room temperature. Data points represent means±s.e.m. from six to nine rats.

Figure 2

Core temperature versus time responses for rats after the administration of vehicle, BRL 44408 (1 mg kg⁻¹) and vehicle, MDMA (20 mg kg⁻¹) alone or following BRL 44408, MDA (20 mg kg⁻¹) or MDEA (20 mg kg⁻¹) at room temperature. Data points represent means±s.e.m. from six to nine rats.

Figure 3

Locomotor activity versus time responses for rats after the administration of vehicle, BRL 44408 (1 mg kg⁻¹) and vehicle, MDMA (20 mg kg⁻¹) alone or following BRL 44408, MDA (20 mg kg⁻¹) or MDEA (20 mg kg⁻¹) at room temperature. Data points represent means±s.e.m. from six to nine rats.

Figure 4

Concentration contractile–response curves for presumed α_1D-adrenoceptor agonist actions of MDEA, MDA and MDMA in aortae from Wistar rats. Each group consisted of five to seven rats. Values are means±s.e.m.

Figure 5

Concentration contractile–response curves for presumed α_1A-adrenoceptor agonist actions of MDEA, MDA and MDMA in whole vas deferens from Wistar rats. Each group consisted of four to five rats. Values are means±s.e.m.

Figure 6

Concentration inhibitory–response curves for presumed α_2A-adrenoceptor agonist actions of MDEA, MDA and MDMA at inhibiting contractions to a single electrical stimulus in epididymal portions of rat vas deferens in the presence of nifedipine (10 μM). Each group consisted of four to eight rats. Values are means±s.e.m. MDMA data are taken from Lavelle et al. (1999).