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Vascular actions of MDMA involve α1 and α2‐adrenoceptors in the anaesthetized rat

John Mcdaid, James R. Docherty

British Journal of Pharmacology June 1, 2001 DOI: 10.1038/sj.bjp.0704094 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Pithed and pentobarbitone anesthetized rats
Interventions MDMA prazosin yohimbine methiothepin ritanserin methoxyidazoxan cocaine
Dose MDMA 1 and 5 mg kg-1; prazosin 0.1 mg kg-1; yohimbine 1 mg kg-1; methiothepin 0.1 mg kg-1; ritanserin 1 mg kg-1; methoxyidazoxan 0.1 mg kg-1; cocaine 1 and 10 mg kg-1
Topics MDMA
Keywords Ritanserin Prazosin Yohimbine Endocrinology Ketanserin Pharmacology Adrenergic antagonist Receptor antagonist
Citations 46
Key findings MDMA's cardiovascular effects in rats involve distinct adrenoceptor mechanisms: initial pressor response via α₂- and possibly α₁-adrenoceptors and 5-HT₂ receptors, a 1-minute pressor component largely α₁-mediated, and a sustained depressor response involving α₂-adrenoceptors.

Abstract

We have investigated the effects of methylenedioxymethamphetamine (MDMA, ‘ecstasy’), i.v., on diastolic blood pressure (DBP) in pithed and pentobarbitone anaesthetized rats. In pithed rats, the non‐selective 5‐HT receptor antagonist methiothepin (0.1 mg kg −1 ) and the α 2 ‐adrenoceptor antagonists methoxyidazoxan and yohimbine (1 mg kg −1 ) showed significant α 1 ‐adrenoceptor antagonist potency, but methiothepin did not show α 2 ‐adrenoceptor antagonist potency. MDMA (1 and 5 mg kg −1 ) produced pressor responses which were significantly reduced by the α 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‐HT 2 receptor antagonist ritanserin (1 mg kg −1 ). In anaesthetized rats, antagonists revealed two phases with three components to the effects of MDMA (5 mg kg −1 ) on DBP: an initial pressor response, a later pressor component at 1 min, the sustained depressor response. Methoxyidazoxan, methiothepin or the combination ritanserin/prazosin significantly reduced the initial pressor response, although neither of the latter compounds alone had any effect. The pressor response to MDMA (5 mg kg −1 ) at 1 min was converted to a depressor response by prazosin and to a lesser extent methiothepin and methoxyidazoxan. 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 blocker cocaine 10 mg kg −1 but not 1 mg kg −1 . However, the most marked reduction in the depressor response was produced by the combination of methoxyidazoxan and cocaine. It is concluded that the initial pressor response to MDMA (5 mg kg −1 ) in anaesthetized rats involves α 2 ‐ and possibly α 1 ‐adrenoceptors and 5‐HT 2 receptors, the pressor component at 1 min is largely α 1 ‐adrenoceptor mediated, and the sustained depressor response involves α 2 ‐adrenoceptors. British Journal of Pharmacology (2001) 133 , 429–437; doi: 10.1038/sj.bjp.0704094

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

Study Year Design Participants
Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) 1987 Experimental study
3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain 1987 Animal experiment
Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells 2006 In vitro laboratory study
Small Changes in Ambient Temperature Cause Large Changes in 3,4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonin Neurotoxicity and Core Body Temperature in the Rat Rats 1998 Experimental study
Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Squirrel monkeys treated with MDMA 1999 Observational cohort

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