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Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain.
Biochem Pharmacol. 1987 Jul 15; 36(14):2297-303.BP

Abstract

3,4-Methylenedioxymethamphetamine (MDMA) is a recently popularized recreational drug, although some have advocated its psychotherapeutic potential. Since the pharmacology of MDMA is largely uncharacterized, the stereochemical profiles of MDMA and some of its homologs were derived on inhibition of synaptosomal uptake of [3H]monoamines and compared to those of amphetamine and the hallucinogenic phenylisopropylamine 2,5-dimethoxy-4-methylamphetamine (DOM). In contrast to the 5-fold stereoselectivity observed with amphetamine, only the S-(+) enantiomer of MDMA and 3,4-methylenedioxyamphetamine (MDA) inhibited [3H]dopamine uptake into striatal synaptosomes. Neither stereoisomer of the alpha-ethyl homolog of MDMA, N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), inhibited [3H]dopamine uptake. The two stereoisomers of amphetamine and the MDMA-related compounds were equipotent in inhibiting [3H]norepinephrine uptake into hypothalamic synaptosomes. Both stereoisomers of MDMA, MDA and MBDB were potent inhibitors of [3H]serotonin uptake into hippocampal synaptosomes, but only S-(+)-amphetamine produced an appreciable inhibition of [3H]serotonin uptake. Neither stereoisomer of DOM inhibited synaptosomal uptake of any [3H]monoamine. These results suggest that MDMA and its homologs may be more closely related to amphetamine rather than to DOM in their biochemical mode of action. The pronounced effects of the methylenedioxy-substituted compounds on [3H]serotonin and [3H]norepinephrine uptake implicate these neurotransmitters in the pharmacological effects of these drugs.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2886126

Citation

Steele, T D., et al. "Stereochemical Effects of 3,4-methylenedioxymethamphetamine (MDMA) and Related Amphetamine Derivatives On Inhibition of Uptake of [3H]monoamines Into Synaptosomes From Different Regions of Rat Brain." Biochemical Pharmacology, vol. 36, no. 14, 1987, pp. 2297-303.
Steele TD, Nichols DE, Yim GK. Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain. Biochem Pharmacol. 1987;36(14):2297-303.
Steele, T. D., Nichols, D. E., & Yim, G. K. (1987). Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain. Biochemical Pharmacology, 36(14), 2297-303.
Steele TD, Nichols DE, Yim GK. Stereochemical Effects of 3,4-methylenedioxymethamphetamine (MDMA) and Related Amphetamine Derivatives On Inhibition of Uptake of [3H]monoamines Into Synaptosomes From Different Regions of Rat Brain. Biochem Pharmacol. 1987 Jul 15;36(14):2297-303. PubMed PMID: 2886126.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain. AU - Steele,T D, AU - Nichols,D E, AU - Yim,G K, PY - 1987/7/15/pubmed PY - 1987/7/15/medline PY - 1987/7/15/entrez SP - 2297 EP - 303 JF - Biochemical pharmacology JO - Biochem Pharmacol VL - 36 IS - 14 N2 - 3,4-Methylenedioxymethamphetamine (MDMA) is a recently popularized recreational drug, although some have advocated its psychotherapeutic potential. Since the pharmacology of MDMA is largely uncharacterized, the stereochemical profiles of MDMA and some of its homologs were derived on inhibition of synaptosomal uptake of [3H]monoamines and compared to those of amphetamine and the hallucinogenic phenylisopropylamine 2,5-dimethoxy-4-methylamphetamine (DOM). In contrast to the 5-fold stereoselectivity observed with amphetamine, only the S-(+) enantiomer of MDMA and 3,4-methylenedioxyamphetamine (MDA) inhibited [3H]dopamine uptake into striatal synaptosomes. Neither stereoisomer of the alpha-ethyl homolog of MDMA, N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB), inhibited [3H]dopamine uptake. The two stereoisomers of amphetamine and the MDMA-related compounds were equipotent in inhibiting [3H]norepinephrine uptake into hypothalamic synaptosomes. Both stereoisomers of MDMA, MDA and MBDB were potent inhibitors of [3H]serotonin uptake into hippocampal synaptosomes, but only S-(+)-amphetamine produced an appreciable inhibition of [3H]serotonin uptake. Neither stereoisomer of DOM inhibited synaptosomal uptake of any [3H]monoamine. These results suggest that MDMA and its homologs may be more closely related to amphetamine rather than to DOM in their biochemical mode of action. The pronounced effects of the methylenedioxy-substituted compounds on [3H]serotonin and [3H]norepinephrine uptake implicate these neurotransmitters in the pharmacological effects of these drugs. SN - 0006-2952 UR - https://www.unboundmedicine.com/medline/citation/2886126/Stereochemical_effects_of_34_methylenedioxymethamphetamine__MDMA__and_related_amphetamine_derivatives_on_inhibition_of_uptake_of_[3H]monoamines_into_synaptosomes_from_different_regions_of_rat_brain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0006-2952(87)90594-6 DB - PRIME DP - Unbound Medicine ER -