Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.
Jakob A. Shimshoni, Ilan Winkler, Ezekiel Golan, David Nutt
Naunyn-Schmiedeberg's Archives of Pharmacology September 20, 2016 DOI: 10.1007/s00210-016-1297-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Human and non-human receptors, transporters, and enzymes |
| Topics | Serotonin MDMA |
| Keywords | Novel compounds Indole analogues Benzofuran analogues New compounds Synthetic compounds Psychoactive compounds Ligands Drug candidates Neurotransmitter transporters Serotonin transporters Dopamine transporters Norepinephrine transporters Monoamine transporters Sert Net Transporter binding sites Brain transporters Neuropharmacology Drug discovery Affinity Mechanism of action Psychopharmacology Drug binding Pharmacodynamics Drug effects Therapeutic potential Brain chemistry Neurochemistry Brain function Central nervous system Cns Neurobiology Neurotransmitters |
| Citations | 23 |
| Key points | All four MDMA analogues displayed higher monoamine receptor/transporter binding affinities and greater agonist activity at 5-HT2a,c receptors compared to MDMA, with 6-MAPB showing a particularly favorable pharmacological profile. |
Abstract
3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT2a,b,c and NEα2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT2a,c receptors as compared to MDMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 8
- Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data? Pharmacology & Therapeutics February 1, 2018
- Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy Journal of Psychopharmacology September 10, 2020
- Bioisosteric analogs of MDMA: Improving the pharmacological profile? Journal of Neurochemistry September 1, 2024
- Novel Benzofuran Derivatives Induce Monoamine Release and Substitute for the Discriminative Stimulus Effects of 3,4-Methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics September 18, 2024
- Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants Drug and Alcohol Dependence Reports August 10, 2023
and 3 more in the library
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