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[3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues.
Eur J Pharmacol. 1991 Jul 23; 200(1):9-16.EJ

Abstract

The ability of several 3,4-methylenedioxymethamphetamine (MDMA) analogues to inhibit the uptake of [3H]serotonin (5-HT), dopamine (DA) and norepinephrine (NE) into synaptosomes was examined. In addition, the ability of the compounds to inhibit the uptake of [3H]5-HT and DA into synaptosomes from rats pretreated with reserpine (5 mg/kg i.p., 16 h pretreatment) was compared to control experiments. All of the test compounds were found to be potent releasers of non-vesicular 5-HT (the reserpine IC50 was significantly smaller than the control IC50). The range of 5-HT inhibitory activity corresponds well to the small range of ED50 values of the test compounds to substitute in drug discrimination experiments with animals trained to discriminate MDMA or S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-aminobutane (S-MBDB) from saline. In contrast, there was a wide range of potency for the inhibition of NE and DA uptake. In addition, several of the analogues appeared to be pure uptake inhibitors of DA while others were found to be releasers of non-vesicular DA. Several of the compounds were very selective for 5-HT over DA or NE uptake inhibition, including 3-methoxy-4-methylamphetamine (MMA) and 5-methoxy-6-methyl-2-aminoindan (MMAI). A correlation was noted between the 5-HT neurotoxic potential of some of the test compounds and their relative ability to induce a release of non-vesicular DA. The potential catechol metabolites of the methylenedioxy-substituted compounds also showed potent monoamine releasing properties, suggesting that metabolism may play a role in the neurotoxic actions of some of these drugs. The present data support the hypothesis that drug-stimulated non-vesicular 5-HT release is primarily responsible for the discriminative cue of MDMA.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

1685125

Citation

Johnson, M P., et al. "[3H]monoamine Releasing and Uptake Inhibition Properties of 3,4-methylenedioxymethamphetamine and P-chloroamphetamine Analogues." European Journal of Pharmacology, vol. 200, no. 1, 1991, pp. 9-16.
Johnson MP, Conarty PF, Nichols DE. [3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues. Eur J Pharmacol. 1991;200(1):9-16.
Johnson, M. P., Conarty, P. F., & Nichols, D. E. (1991). [3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues. European Journal of Pharmacology, 200(1), 9-16.
Johnson MP, Conarty PF, Nichols DE. [3H]monoamine Releasing and Uptake Inhibition Properties of 3,4-methylenedioxymethamphetamine and P-chloroamphetamine Analogues. Eur J Pharmacol. 1991 Jul 23;200(1):9-16. PubMed PMID: 1685125.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues. AU - Johnson,M P, AU - Conarty,P F, AU - Nichols,D E, PY - 1991/7/23/pubmed PY - 1991/7/23/medline PY - 1991/7/23/entrez SP - 9 EP - 16 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 200 IS - 1 N2 - The ability of several 3,4-methylenedioxymethamphetamine (MDMA) analogues to inhibit the uptake of [3H]serotonin (5-HT), dopamine (DA) and norepinephrine (NE) into synaptosomes was examined. In addition, the ability of the compounds to inhibit the uptake of [3H]5-HT and DA into synaptosomes from rats pretreated with reserpine (5 mg/kg i.p., 16 h pretreatment) was compared to control experiments. All of the test compounds were found to be potent releasers of non-vesicular 5-HT (the reserpine IC50 was significantly smaller than the control IC50). The range of 5-HT inhibitory activity corresponds well to the small range of ED50 values of the test compounds to substitute in drug discrimination experiments with animals trained to discriminate MDMA or S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-aminobutane (S-MBDB) from saline. In contrast, there was a wide range of potency for the inhibition of NE and DA uptake. In addition, several of the analogues appeared to be pure uptake inhibitors of DA while others were found to be releasers of non-vesicular DA. Several of the compounds were very selective for 5-HT over DA or NE uptake inhibition, including 3-methoxy-4-methylamphetamine (MMA) and 5-methoxy-6-methyl-2-aminoindan (MMAI). A correlation was noted between the 5-HT neurotoxic potential of some of the test compounds and their relative ability to induce a release of non-vesicular DA. The potential catechol metabolites of the methylenedioxy-substituted compounds also showed potent monoamine releasing properties, suggesting that metabolism may play a role in the neurotoxic actions of some of these drugs. The present data support the hypothesis that drug-stimulated non-vesicular 5-HT release is primarily responsible for the discriminative cue of MDMA. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/1685125/[3H]monoamine_releasing_and_uptake_inhibition_properties_of_34_methylenedioxymethamphetamine_and_p_chloroamphetamine_analogues_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0014-2999(91)90659-E DB - PRIME DP - Unbound Medicine ER -