Investigation of the prejunctional alpha(2)-adrenoceptor mediated actions of MDMA in rat atrium and vas deferens

1 We have investigated the effects of methylenedioxymethamphetamine (MDMA, 'ecstasy') on peripheral noradrenergic neurotransmission in the rat. 2 In rat atrial slices pre-incubated with [H-3]-noradrenaline and in the pr esence of desipramine (1 mu M) to prevent effects of MDMA on basal outflow of tritium, MDMA (10 mu M) significantly inhibited the release of tritium e voked by short trains of six pulses at 100 Hz every 10 s for 3 min. This ef fect did not occur in the presence of the alpha(2)-adrenoceptor antagonist yohimbine (1 mu M). 3 In epididymal portions of rat vas deferens in the presence of nifedipine (10 mu M), MDMA produced a concentration-dependent inhibition of single pul se nerve stimulation-evoked contractions with a pD(2) of 5.88 +/- 0.16 (n = 4). Inhibitory effects of MDMA were antagonized by the alpha(2)-adrenocept or antagonist yohimbine (0.3 mu M), but not by the 5-hydroxytryptamine rece ptor antagonist cyanopindolol in a concentration (1 mu M) which markedly an tagonized the inhibitory actions of the 5-HT-1 receptor agonist 5-carboxami dotryptamine. 4 In prostatic portions of rat vas deferens in the presence of cocaine (3 m u M), MDMA produced a concentration-dependent inhibition of single pulse ne rve stimulation-evoked contractions with a pD(2) of 5.12 +/- 0.21 (n = 4). In the absence of cocaine, only the highest concentrations of MDMA (30 mu M ) produced an inhibition, but the az-adrenoceptor antagonist yohimbine (0.3 mu M) converted response to MDMA from inhibition to potentiation of the st imulation-evoked contraction. 5 In radioligand binding studies, MDMA showed similar affinities for alpha( 2B), alpha(2C) and alpha(2D)-adrenoceptor sites, with pK(i) values of 5.14 +/- 0.16, 5.11 +/- 0.05 and 5.31 +/- 0.14, respectively. 6 It is concluded that MDMA has significant alpha(2)-adrenoceptor agonist a ctions.