Article date: April 2006
By: Sotiria Bexis, James R Docherty in Volume 147, Issue 8, pages 926-934
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 α2A‐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 (α1D) and vas deferens (α1A) was MDA>MDMA>MDEA, with MDEA acting as an α1‐adrenoceptor antagonist with a pKB of 4.79±0.12 (n=4) in aorta.
The order of potency for prejunctional inhibition of stimulation‐evoked contractions in rat vas deferens (α2A‐adrenoceptor mediated) was MDA>MDMA>MDEA.
Blood pressure actions of the three amphetamine derivatives may be at least partly due to α1‐adrenoceptor agonism or antagonism. The reversal of the hypothermic actions are at least partly due to α2A‐adrenoceptor agonism since the hypothermic response was more prolonged with MDEA which exhibits low α2A‐adrenoceptor potency, and effects of MDMA after α2A‐adrenoceptor antagonism were similar to those of MDEA.
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 α2A‐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 (α1D) and vas deferens (α1A) was MDA>MDMA>MDEA, with MDEA acting as an α1‐adrenoceptor antagonist with a pKB of 4.79±0.12 (n=4) in aorta.
The order of potency for prejunctional inhibition of stimulation‐evoked contractions in rat vas deferens (α2A‐adrenoceptor mediated) was MDA>MDMA>MDEA.
Blood pressure actions of the three amphetamine derivatives may be at least partly due to α1‐adrenoceptor agonism or antagonism. The reversal of the hypothermic actions are at least partly due to α2A‐adrenoceptor agonism since the hypothermic response was more prolonged with MDEA which exhibits low α2A‐adrenoceptor potency, and effects of MDMA after α2A‐adrenoceptor antagonism were similar to those of MDEA.
British Journal of Pharmacology (2006) 147, 926–934. doi:10.1038/sj.bjp.0706688
DOI: 10.1038/sj.bjp.0706688
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