Investigation of the prejunctional α2‐adrenoceptor mediated actions of MDMA in rat atrium and vas deferens
British Journal of Pharmacology – November 01, 1999
Source: OpenAlex
Summary
MDMA, commonly known as ecstasy, significantly inhibits noradrenaline release in rat atrial slices, showcasing its powerful effects on neurotransmission. In experiments with 4 rats, MDMA (10 μM) reduced tritium release during nerve stimulation, an effect reversed by the α2-adrenoceptor antagonist yohimbine (1 μM). In the vas deferens, MDMA also inhibited contractions in a concentration-dependent manner, with pD2 values of 5.88 and 5.12. These findings highlight MDMA's role as an α2-adrenoceptor agonist, influencing neurotransmitter activity and potential clinical implications in internal medicine and pharmacology.
Abstract
We have investigated the effects of methylenedioxymethamphetamine (MDMA, ‘ecstasy’) on peripheral noradrenergic neurotransmission in the rat. In rat atrial slices pre‐incubated with [ 3 H]‐noradrenaline and in the presence of desipramine (1 μ M ) to prevent effects of MDMA on basal outflow of tritium, MDMA (10 μ M ) significantly inhibited the release of tritium evoked by short trains of six pulses at 100 Hz every 10 s for 3 min. This effect did not occur in the presence of the α 2 ‐adrenoceptor antagonist yohimbine (1 μ M ). In epididymal portions of rat vas deferens in the presence of nifedipine (10 μ M ), MDMA produced a concentration‐dependent inhibition of single pulse nerve stimulation‐evoked contractions with a pD 2 of 5.88±0.16 ( n =4). Inhibitory effects of MDMA were antagonized by the α 2 ‐adrenoceptor antagonist yohimbine (0.3 μ M ), but not by the 5‐hydroxytryptamine receptor antagonist cyanopindolol in a concentration (1 μ M ) which markedly antagonized the inhibitory actions of the 5‐HT‐1 receptor agonist 5‐carboxamidotryptamine. In prostatic portions of rat vas deferens in the presence of cocaine (3 μ M ), MDMA produced a concentration‐dependent inhibition of single pulse nerve stimulation‐evoked contractions with a pD 2 of 5.12±0.21 ( n =4). In the absence of cocaine, only the highest concentration of MDMA (30 μ M ) produced an inhibition, but the α 2 ‐adrenoceptor antagonist yohimbine (0.3 μ M ) converted the response to MDMA from inhibition to potentiation of the stimulation‐evoked contraction. In radioligand binding studies, MDMA showed similar affinities for α 2B , α 2C and α 2D ‐adrenoceptor sites, with pK i values of 5.14±0.16, 5.11±0.05 and 5.31±0.14, respectively. It is concluded that MDMA has significant α 2 ‐adrenoceptor agonist actions. British Journal of Pharmacology (1999) 128 , 975–980; doi: 10.1038/sj.bjp.0702875