Vascular actions of MDMA involve alpha(1) and alpha(2)-adrenoceptors in the anaesthetized rat

1 We have investigated the effects of methylenedioxymethamphetamine (MDMA, 'ecstasy'), i.v., on diastolic blood pressure (DBP) in pithed and pentobarb itone anaesthetized rats. 2 In pithed rats, the non-selective 5-HT receptor antagonist methiothepin ( 0.1 mg kg(-1)) and the alpha (2)-adrenoceptor antagonists methoxyidazoxan a nd yohimbine (1 mg kg(-1)) showed significant alpha (1)-adrenoceptor antago nist potency, but methiothepin did not show alpha (2)-adrenoceptor antagoni st potency. MDMA (I and 5 mg kg(-1)) produced presser responses which were significantly reduced by the alpha (1)-adrenoceptor antagonist prazosin (0. 1 mg kg(-1)), yohimbine (1 mg kg(-1)) or methiothepin (0.1 mg kg(-1)), but not by the 5-HT2 receptor antagonist ritanserin (1 mg kg(-1)). 3 In anaesthetized rats, antagonists revealed two phases with three compone nts to the effects of MDMA (5 mg kg(-1)) on DBP: an initial presser respons e, a later presser component at 1 min, the sustained depressor response. Me thoxyidazoxan, methiothepin or the combination ritanserin/prazosin signific antly reduced the initial presser response, although neither of the latter compounds alone had any effect. 4 The presser response to MDMA (5 mg kg(-1)) at 1 min was converted to a de pressor response by prazosin and to a lesser extent methiothepin and methox yidazoxan. 5 The depressor response to MDMA (5 mg kg(-1)) was significantly reduced by methoxyidazoxan (0.1 mg kg(-1)), and by the noradrenaline re-uptake blocke r cocaine 10 mg kg(-1) but not I mg kg(-1) However, the most marked reducti on in the depressor response was produced by the combination of methoxyidaz oxan and cocaine. 6 It is concluded that the initial presser response to MDMA (5 mg kg(-1)) i n anaesthetized rats involves alpha (2)- and possibly alpha (1)-adrenocepto rs and 5-HT2 receptors, the presser component at 1 min is largely alpha (1) -adrenoceptor mediated, and the sustained depressor response involves alpha (2)-adrenoceptors.