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Comparative effects of substituted amphetamines (PMA, MDMA, and METH) on monoamines in rat caudate: a microdialysis study.
Ann N Y Acad Sci. 2002 Jun; 965:410-20.AN

Abstract

Paramethoxyamphetamine (PMA) is a methoxylated phenethylamine derivative that has been used illicitly in Australia since 1994. PMA is also becoming popular at rave parties in the United States. PMA raised concern when a series of fatalities resulted after its use in South Australia, where it was marketed as "ecstasy," which is the colloquial name for MDMA. In the present study, we evaluated the comparative neurotoxicity of substituted amphetamines in rats. Extracellular levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were assayed in the caudate of freely moving rats using microdialysis and HPLC-EC. Dialysates were assayed every 20 minutes for 4 hours after an intraperitoneal (i.p.) injection of PMA (2.5, 5, 10, 20 mg/kg), MDMA (10 and 20 mg/kg), or METH (2.5 mg/kg). METH produced a significant increase in extracellular DA (700%), and significant decreases in extracellular DOPAC and HVA (30% and 50%), with no detectable changes in either 5-HT or 5-HIAA. MDMA produced significant increases in DA (700% at 10 mg/kg and 950% at 20 mg/kg) and decreases in DOPAC (15% for both 10 and 20 mg/kg), and HVA (50% at 10 mg/kg and 35% at 20 mg/kg). MDMA also increased 5-HT (350% at 10, and 575% at 20 mg/kg), and decreased 5-HIAA to 60% for both dose levels. PMA produced no detectable increases in DA at dose levels of 2.5, 5, or 10 mg/kg, but significantly increased DA (975%) at a dose of 20 mg/kg. However, PMA significantly decreased DOPAC at all dose levels (75% at 2.5; 40% at 5; 30% at 10; 10% at 20 mg/kg), with comparable decreases in HVA at all dose levels. PMA also produced significant increases in 5-HT at 10 and 20 mg/kg (350% for both dose levels), with no detectable changes in 5-HT at 2.5 or 5 mg/kg. All dose levels of PMA significantly decreased 5-HIAA (50 to 70%). These data suggest that PMA, like MDMA and METH, is capable of producing dopaminergic and serotonergic neurotoxicity.

Authors+Show Affiliations

Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, Arkansas 72079, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12105116

Citation

Gough, Bobby, et al. "Comparative Effects of Substituted Amphetamines (PMA, MDMA, and METH) On Monoamines in Rat Caudate: a Microdialysis Study." Annals of the New York Academy of Sciences, vol. 965, 2002, pp. 410-20.
Gough B, Imam SZ, Blough B, et al. Comparative effects of substituted amphetamines (PMA, MDMA, and METH) on monoamines in rat caudate: a microdialysis study. Ann N Y Acad Sci. 2002;965:410-20.
Gough, B., Imam, S. Z., Blough, B., Slikker, W., & Ali, S. F. (2002). Comparative effects of substituted amphetamines (PMA, MDMA, and METH) on monoamines in rat caudate: a microdialysis study. Annals of the New York Academy of Sciences, 965, 410-20.
Gough B, et al. Comparative Effects of Substituted Amphetamines (PMA, MDMA, and METH) On Monoamines in Rat Caudate: a Microdialysis Study. Ann N Y Acad Sci. 2002;965:410-20. PubMed PMID: 12105116.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative effects of substituted amphetamines (PMA, MDMA, and METH) on monoamines in rat caudate: a microdialysis study. AU - Gough,Bobby, AU - Imam,Syed Z, AU - Blough,Bruce, AU - Slikker,William,Jr AU - Ali,Syed F, PY - 2002/7/10/pubmed PY - 2002/8/3/medline PY - 2002/7/10/entrez SP - 410 EP - 20 JF - Annals of the New York Academy of Sciences JO - Ann N Y Acad Sci VL - 965 N2 - Paramethoxyamphetamine (PMA) is a methoxylated phenethylamine derivative that has been used illicitly in Australia since 1994. PMA is also becoming popular at rave parties in the United States. PMA raised concern when a series of fatalities resulted after its use in South Australia, where it was marketed as "ecstasy," which is the colloquial name for MDMA. In the present study, we evaluated the comparative neurotoxicity of substituted amphetamines in rats. Extracellular levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were assayed in the caudate of freely moving rats using microdialysis and HPLC-EC. Dialysates were assayed every 20 minutes for 4 hours after an intraperitoneal (i.p.) injection of PMA (2.5, 5, 10, 20 mg/kg), MDMA (10 and 20 mg/kg), or METH (2.5 mg/kg). METH produced a significant increase in extracellular DA (700%), and significant decreases in extracellular DOPAC and HVA (30% and 50%), with no detectable changes in either 5-HT or 5-HIAA. MDMA produced significant increases in DA (700% at 10 mg/kg and 950% at 20 mg/kg) and decreases in DOPAC (15% for both 10 and 20 mg/kg), and HVA (50% at 10 mg/kg and 35% at 20 mg/kg). MDMA also increased 5-HT (350% at 10, and 575% at 20 mg/kg), and decreased 5-HIAA to 60% for both dose levels. PMA produced no detectable increases in DA at dose levels of 2.5, 5, or 10 mg/kg, but significantly increased DA (975%) at a dose of 20 mg/kg. However, PMA significantly decreased DOPAC at all dose levels (75% at 2.5; 40% at 5; 30% at 10; 10% at 20 mg/kg), with comparable decreases in HVA at all dose levels. PMA also produced significant increases in 5-HT at 10 and 20 mg/kg (350% for both dose levels), with no detectable changes in 5-HT at 2.5 or 5 mg/kg. All dose levels of PMA significantly decreased 5-HIAA (50 to 70%). These data suggest that PMA, like MDMA and METH, is capable of producing dopaminergic and serotonergic neurotoxicity. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/12105116/Comparative_effects_of_substituted_amphetamines__PMA_MDMA_and_METH__on_monoamines_in_rat_caudate:_a_microdialysis_study_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0077-8923&date=2002&volume=965&spage=410 DB - PRIME DP - Unbound Medicine ER -