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Potentiation of 3,4-methylenedioxymethamphetamine-induced 5-HT release in the rat substantia nigra by clorgyline, a monoamine oxidase A inhibitor.
Clin Exp Pharmacol Physiol 2007; 34(10):1051-7CE

Abstract

1. It is well established that the commonly used recreational drugs 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and para-methoxyamphetamine (PMA) facilitate the release and prevent the reuptake of 5-hydroxytryptamine (5-HT, serotonin). Although these drugs have similar potencies for their abilities to increase the release and inhibit the re-uptake of 5-HT, PMA has greater potency as an inhibitor of monoamine oxidase (MAO)-A. 2. The present study compared the abilities of PMA and MDMA to increase extracellular 5-HT concentrations in animals with functional MAO-A and when MAO-A activity was inhibited by clorgyline. 3. Samples of extracellular fluid from rat substantia nigra were collected using microdialysis and then analysed for 5-HT and 5-hydroxyindol acetic acid (5-HIAA) by high-performance liquid chromatography coupled with electrochemical detection. The 5-HT-mediated effects on body temperature and behaviour were also recorded. Rats were pretreated with saline or 10 mg/kg, i.p., clorgyline and, 24 h later, injected with 10 mg/kg MDMA, PMA or saline. 4. Both MDMA and PMA produced significant increases in extracellular 5-HT concentrations (482 +/- 83 and 726 +/- 287%, respectively; P < 0.05). Rats treated with PMA and MDMA displayed significantly increased 5-HT-related behavours (P < 0.05). Furthermore, only MDMA was capable of producing additional significant increases in 5-HT concentrations (1033 +/- 131%; P < 0.01) when coadministered with clorgyline. 5. The results of the present study suggest that PMA and MDMA are similar in their abilities to increase extracellular 5-HT levels in animals with functional MAO-A activity. However, coadministration of these substituted amphetamines with an MAO-A inhibitor causes significant potentiation in the ability to increase extracellular levels of 5-HT for MDMA, but not PMA.

Authors+Show Affiliations

Discipline of Pharmacology, School of Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17714093

Citation

Hewton, Ryan, et al. "Potentiation of 3,4-methylenedioxymethamphetamine-induced 5-HT Release in the Rat Substantia Nigra By Clorgyline, a Monoamine Oxidase a Inhibitor." Clinical and Experimental Pharmacology & Physiology, vol. 34, no. 10, 2007, pp. 1051-7.
Hewton R, Salem A, Irvine RJ. Potentiation of 3,4-methylenedioxymethamphetamine-induced 5-HT release in the rat substantia nigra by clorgyline, a monoamine oxidase A inhibitor. Clin Exp Pharmacol Physiol. 2007;34(10):1051-7.
Hewton, R., Salem, A., & Irvine, R. J. (2007). Potentiation of 3,4-methylenedioxymethamphetamine-induced 5-HT release in the rat substantia nigra by clorgyline, a monoamine oxidase A inhibitor. Clinical and Experimental Pharmacology & Physiology, 34(10), pp. 1051-7.
Hewton R, Salem A, Irvine RJ. Potentiation of 3,4-methylenedioxymethamphetamine-induced 5-HT Release in the Rat Substantia Nigra By Clorgyline, a Monoamine Oxidase a Inhibitor. Clin Exp Pharmacol Physiol. 2007;34(10):1051-7. PubMed PMID: 17714093.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potentiation of 3,4-methylenedioxymethamphetamine-induced 5-HT release in the rat substantia nigra by clorgyline, a monoamine oxidase A inhibitor. AU - Hewton,Ryan, AU - Salem,Abdallah, AU - Irvine,Rodney J, PY - 2007/8/24/pubmed PY - 2007/10/4/medline PY - 2007/8/24/entrez SP - 1051 EP - 7 JF - Clinical and experimental pharmacology & physiology JO - Clin. Exp. Pharmacol. Physiol. VL - 34 IS - 10 N2 - 1. It is well established that the commonly used recreational drugs 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and para-methoxyamphetamine (PMA) facilitate the release and prevent the reuptake of 5-hydroxytryptamine (5-HT, serotonin). Although these drugs have similar potencies for their abilities to increase the release and inhibit the re-uptake of 5-HT, PMA has greater potency as an inhibitor of monoamine oxidase (MAO)-A. 2. The present study compared the abilities of PMA and MDMA to increase extracellular 5-HT concentrations in animals with functional MAO-A and when MAO-A activity was inhibited by clorgyline. 3. Samples of extracellular fluid from rat substantia nigra were collected using microdialysis and then analysed for 5-HT and 5-hydroxyindol acetic acid (5-HIAA) by high-performance liquid chromatography coupled with electrochemical detection. The 5-HT-mediated effects on body temperature and behaviour were also recorded. Rats were pretreated with saline or 10 mg/kg, i.p., clorgyline and, 24 h later, injected with 10 mg/kg MDMA, PMA or saline. 4. Both MDMA and PMA produced significant increases in extracellular 5-HT concentrations (482 +/- 83 and 726 +/- 287%, respectively; P < 0.05). Rats treated with PMA and MDMA displayed significantly increased 5-HT-related behavours (P < 0.05). Furthermore, only MDMA was capable of producing additional significant increases in 5-HT concentrations (1033 +/- 131%; P < 0.01) when coadministered with clorgyline. 5. The results of the present study suggest that PMA and MDMA are similar in their abilities to increase extracellular 5-HT levels in animals with functional MAO-A activity. However, coadministration of these substituted amphetamines with an MAO-A inhibitor causes significant potentiation in the ability to increase extracellular levels of 5-HT for MDMA, but not PMA. SN - 0305-1870 UR - https://www.unboundmedicine.com/medline/citation/17714093/Potentiation_of_34_methylenedioxymethamphetamine_induced_5_HT_release_in_the_rat_substantia_nigra_by_clorgyline_a_monoamine_oxidase_A_inhibitor_ L2 - https://doi.org/10.1111/j.1440-1681.2007.04734.x DB - PRIME DP - Unbound Medicine ER -