Investigation of the prejunctional α2‐adrenoceptor mediated actions of MDMA in rat atrium and vas deferens
Aisling Lavelle, Valerie Honner, James R. Docherty
British Journal of Pharmacology November 1, 1999 DOI: 10.1038/sj.bjp.0702875 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory experiment Peer reviewed |
|---|---|
| Population | Rat atrial slices and vas deferens tissue |
| Intervention | MDMA |
| Dose | 10 μM (atrial slices); concentration-dependent (0.3-30 μM in vas deferens) |
| Topics | MDMA |
| Keywords | Yohimbine Vas deferens Endocrinology Phentolamine Antagonist Prazosin Stimulation Pharmacology Hypogastric nerve |
| Citations | 55 |
| Key findings | MDMA acts as an agonist at alpha-2 adrenoceptors in rat peripheral noradrenergic nerves, inhibiting neurotransmitter release and smooth muscle contractions. |
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
Comparable studies
Other experimental studies on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| Oxytocin-dependent reopening of a social reward learning critical period with MDMA | 2019 | Experimental study | |
| Effects of certain hallucinogenic amphetamine analogs on the release of [3H]-serotonin from rat brain synaptosomes Rat whole brain synaptosomes | 1982 | Experimental study |
Citations in the library
Cited by 25
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- The 21st century psychedelic renaissance: heroic steps forward on the back of an elephant Psychopharmacology August 23, 2017
- The role of monoamines in the changes in body temperature induced by 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives British Journal of Pharmacology March 3, 2010
- Effects of MDMA, MDA and MDEA on blood pressure, heart rate, locomotor activity and body temperature in the rat involveα‐adrenoceptors British Journal of Pharmacology February 20, 2006
- A developmental comparison of the neurobehavioral effects of ecstasy (MDMA) Neurotoxicology and Teratology October 21, 2006
and 20 more in the library
Cites 8
- 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. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- 'Eve' and 'Ecstasy'. A report of five deaths associated with the use of MDEA and MDMA JAMA March 27, 1987
- 'Eve' and 'Ecstasy' JAMA March 27, 1987
- In vivo evidence for free radical involvement in the degeneration of rat brain 5‐HT following administration of MDMA (‘ecstasy’) and p‐chloroamphetamine but not the degeneration following fenfluramine British Journal of Pharmacology July 1, 1997
- Review of the pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA or "Ecstasy"). Psychopharmacology June 1995
and 3 more in the library