Behavioral effects of the highly selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan.
European Journal of Pharmacology June 2, 1994 DOI: 10.1016/0014-2999(94)90051-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Drug discrimination study with behavioral observation Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MMAI MDMA (+)-MBDB (+)-amphetamine LSD (+)-fenfluramine p-chloroamphetamine p-chlorophenylalanine fluoxetine paroxetine ketanserin methiothepin pindolol yohimbine haloperidol |
| Dose | 1.71 mg/kg (MMAI), 1.75 mg/kg (MDMA), 1.75 mg/kg ((+)-MBDB), 1 mg/kg ((+)-amphetamine), 0.08 mg/kg (LSD), 2 x 200 mg/kg (p-chlorophenylalanine), 10 mg/kg (fluoxetine), 2.5 mg/kg (paroxetine), 5, 10, or 20 mg/kg (MMAI for behavioral syndrome) |
| Topics | 5-MeO-DMT Serotonin |
| Citations | 32 |
| Key points | MMAI acts as a selective serotonin releaser, lacking amphetamine-like or LSD-like effects, and its discriminative stimulus depends on endogenous serotonin. |
Abstract
The behavioral effects of 5-methoxy-6-methyl-2-aminoindan (MMAI) were examined using the drug discrimination procedure and direct observation for classification of the characteristic syndrome induced by MMAI. The stimulus effects of MMAI were studied in 5 different groups of rats trained to discriminate MMAI (1.71 mg/kg; 8 microM/kg), MDMA (3,4-methylenedioxymethamphetamine; 1.75 mg/kg; 7.6 microM/kg), (+)-MBDB ((+)-N-methylamino-(1,3-benzodioxo-5-yl)-2-butanamine; 1.75 mg/kg; 7.18 microM/kg), (+)-amphetamine (1 mg/kg; 5.4 microM/kg), or LSD ((+)-lysergic acid diethylamide tartrate; 0.08 mg/kg; 186 nM/kg) from saline. In substitution tests in rats trained to discriminate MMAI from saline, all the compounds which fully mimicked MMAI were serotonin (5-hydroxytryptamine, 5-HT) releasing agents. This substitution is symmetrical for MDMA and (+)-MBDB. Nevertheless, the dose-response curve of MMAI is parallel to those of (+)-fenfluramine (m-trifluoromethyl-N-ethylamphetamine) and p-chloroamphetamine. The results also show that MMAI lacks amphetamine-like and LSD-like discriminative stimulus effects, suggesting that MMAI is neither a psychostimulant nor a hallucinogen. Tests of the discriminability of MMAI after 5-HT depletion with the selective serotonin synthesis inhibitor, p-chlorophenylalanine (2 x 200 mg/kg i.p., pretreatment 72 h before test), showed only saline appropriate responding. Prolonged block (ca. 1 week) of the MMAI cue by p-chlorophenylalanine further supports the conclusion that endogenous 5-HT is essential for MMAI discrimination. Fluoxetine (10 mg/kg) or paroxetine (2.5 mg/kg), both selective 5-HT uptake inhibitors, reduced the discriminability of MMAI to 40% and 50%, respectively. None of the antagonists (ketanserin, methiothepin, pindolol, yohimbine, haloperidol) used in antagonism tests inhibited the stimulus properties of MMAI. These results and data from radioligand binding studies support the conclusion that direct activation or inhibition of known neurotransmitter receptors did not play a significant role in the discriminative cue of MMAI. The administration of 5, 10, or 20 mg/kg of MMAI to rats induced a behavioral syndrome consisting of hypolocomotion with accompanying catalepsy-like posture, turning, Straub tail, flat body posture, and suppressed sleeping time. In general, this is qualitatively similar to what is seen after administration of 5-HT precursors or 5-HT receptor agonists. In conclusion, the data from the drug discrimination study and the behavioral syndrome induced by MMAI suggest that MMAI is a potential selective releaser of serotonin.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 11
- Synthetic Aminoindanes: A Summary of Existing Knowledge Frontiers in Psychiatry November 17, 2017
- 2-Aminoindan and its Ring-Substituted Derivatives Interact with Plasma Membrane Monoamine Transporters and α2-Adrenergic Receptors Psychopharmacology March 1, 2019
- Evaluating the abuse potential of psychedelic drugs as part of the safety pharmacology assessment for medical use in humans. Neuropharmacology November 2018
- Pharmacological profile of mephedrone analogs and related new psychoactive substances. Neuropharmacology May 15, 2018
- An animal model of schizophrenia based on chronic LSD administration: old idea, new results. Neuropharmacology February 23, 2011
and 6 more in the library
Cites 13
- The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proceedings of the National Academy of Sciences March 1, 1992
- 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class Journal of Medicinal Chemistry October 1, 1986
- p-methylthioamphetamine is a potent new non-neurotoxic serotonin-releasing agent. European Journal of Pharmacology December 8, 1992
- 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) Journal of Medicinal Chemistry May 1, 1991
and 8 more in the library