Synthesis and pharmacological examination of 1-(3-methoxy-4-methylphenyl)-2-aminopropane and 5-methoxy-6-methyl-2-aminoindan: similarities to 3,4-(methylenedioxy)methamphetamine (MDMA)
Michael P. Johnson, Stewart Frescas, Robert Oberlender, David E. Nichols
Journal of Medicinal Chemistry May 1, 1991 DOI: 10.1021/jm00109a020 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | 1-(3-methoxy-4-methyphenyl)-2-aminopropane (6) 5-methoxy-6-methyl-2-aminoindan (11) |
| Dose | 10 or 20 mg/kg, sc (single high dose); 20 mg/kg, sc, twice a day for 4 days (subacute) |
| Duration | Single high dose with one-week follow-up; subacute dosing (20 mg/kg, sc, twice a day for 4 days) with two-week follow-up |
| Measures | drug-discrimination (substitution), [3H]-5-HT uptake, [3H]paroxetine binding, rat brain monoamine levels |
| Topics | MDMA 5-MeO-DMT |
| Keywords | Methylenedioxy Methamphetamine Stereochemistry Pharmacology Organic chemistry |
| Citations | 53 |
| Key points | Compounds 6 and 11 mimic the behavioral effects of MDMA-like drugs but do not induce serotonin neurotoxicity. |
Abstract
The racemate and the enantiomers of 1-(3-methoxy-4-methyphenyl)-2- aminopropane (6) and racemic 5-methoxy-6-methyl-2-aminoindan (11) were tested for stimulus generalization in the two-lever drug-discrimination paradigm. Both 6 and 11 were found to substitute with high potency in 3,4-(methylenedioxy)methamphetamine (1) and (S)-1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (2) trained rats. In the latter assay, both enantiomers of 6 had identical potencies, but their dose-response curves were not parallel. Racemic 6, but not 11, partially substituted for LSD. Racemic 6 and 11 did not substitute in (S)-amphetamine-trained rats. All of the test compounds were potent inhibitors of [3H]-5-HT uptake into synaptosomes in vitro, with the S enantiomer of 6 being most active. Rat brain monoamine levels were unaltered 1 week following a single high dose (10 or 20 mg/kg, sc) of 6 or 11, or two weeks following a subacute dosing regimen (20 mg/kg, sc, twice a day for 4 days). In addition, radioligand-binding parameters in rat brain homogenate with the 5-HT uptake inhibitor [3H]paroxetine were unchanged after subacute dosing with either racemic 6 or 11. The results indicate that compounds 6 and 11 have animal behavioral pharmacology similar to the methylenedioxy compounds 1 and 2, but that they do not induce the serotonin neurotoxicity that has been observed for the latter two drugs.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- p-methylthioamphetamine is a potent new non-neurotoxic serotonin-releasing agent. European Journal of Pharmacology December 8, 1992
- MDAI (5,6‐methylenedioxy‐2‐aminoindane; 6,7‐dihydro‐5H‐cyclopenta[f][1,3]benzodioxol‐6‐amine; ‘sparkle’; ‘mindy’) toxicity: a brief overview and update Human Psychopharmacology: Clinical and Experimental July 1, 2013
- Initial characterization of PMMA as a discriminative stimulus. Pharmacology, Biochemistry, and Behavior 1997
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