RTI-83
Chemical compound
title: "RTI-83" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["tropanes", "rti-compounds", "serotonin–dopamine-reuptake-inhibitors", "sympathomimetic-amines", "methyl-esters", "ethyl-compounds", "para-phenylene-compounds"] description: "Chemical compound" topic_path: "general/tropanes" source: "https://en.wikipedia.org/wiki/RTI-83" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0
::summary Chemical compound ::
::data[format=table title="Infobox drug"]
| Field | Value |
|---|---|
| IUPAC_name | Methyl (1R,2S,3S,5S)-3-(4-ethylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate |
| image | Phenyltropane 11g.svg |
| image_class | skin-invert-image |
| CAS_number | 155337-52-3 |
| PubChem | 9882384 |
| ChemSpiderID | 8599598 |
| UNII | 3LPN4HUW1C |
| ChEMBL | 1947090 |
| synonyms | RTI-4229-83 |
| C | 18 |
| smiles | CCc3ccc(cc3)C(C1C(=O)OC)CC2CCC1N2C |
| StdInChI | 1S/C18H25NO2/c1-4-12-5-7-13(8-6-12)15-11-14-9-10-16(19(14)2)17(15)18(20)21-3/h5-8,14-17H,4,9-11H2,1-3H3/t14-,15+,16+,17-/m0/s1 |
| StdInChIKey | UAMCGXVVAUEEEU-HZMVEIRTSA-N |
| :: |
| IUPAC_name = Methyl (1R,2S,3S,5S)-3-(4-ethylphenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate | image = Phenyltropane 11g.svg | image_class = skin-invert-image
| tradename =
| CAS_number = 155337-52-3 | ATC_prefix = | ATC_suffix = | PubChem = 9882384 | ChemSpiderID = 8599598 | UNII = 3LPN4HUW1C | ChEMBL = 1947090 | synonyms = RTI-4229-83
| C=18 | H=25 | N=1 | O=2 | smiles = CCc3ccc(cc3)C(C1C(=O)OC)CC2CCC1N2C | StdInChI = 1S/C18H25NO2/c1-4-12-5-7-13(8-6-12)15-11-14-9-10-16(19(14)2)17(15)18(20)21-3/h5-8,14-17H,4,9-11H2,1-3H3/t14-,15+,16+,17-/m0/s1 | StdInChIKey = UAMCGXVVAUEEEU-HZMVEIRTSA-N
RTI-83 ((–)-2β-carbomethoxy-3β-(4-ethylphenyl)tropane) is a phenyltropane derivative which represents a rare example of an SDRI or serotonin-dopamine reuptake inhibitor, a drug which inhibits the reuptake of the neurotransmitters serotonin and dopamine, while having little or no effect on the reuptake of the related neurotransmitter noradrenaline. With a binding affinity (Ki) of 55 nM at DAT and 28.4 nM at SERT but only 4030 nM at NET, RTI-83 has reasonable selectivity for DAT/SERT over NET
::figure[src="https://upload.wikimedia.org/wikipedia/commons/e/eb/Phenyltropane_11w.svg" caption="''cis''-propenyl analogue (RTI-304)]]{{clear left}}"] ::
However, further research has shown that by extending the ethyl chain even better selectivity can be achieved, with the 4′-(cis-propenyl) analogue having Ki values of 15 nM at DAT and 7.1 nM at SERT, vs 2800 nM at NET. However RTI-436 has an even better selectivity for DAT over NET (3.09 nM @ DAT and 1,960 nM @ NET, or a NET/DAT ratio of 634.3, but with lesser DAT/SERT equivalent potency with a ratio between them of 108) and RTI-88 has a still better ratio (984 NET/DAT with additionally having less selectivity than the former compound between DAT/SERT and having a more even spread of potency with the ratio between DAT and SERT being 88).
::data[format=table title="Binding comparison between phenyltropanes with high NET/DAT selectivity ratios"]
| Compound | DAT | 5-HTT | NET | Selectivity | Selectivity |
|---|---|---|---|---|---|
| RTI-83 | 55 ± 2.1 | 28.4 ± 3.8 | 4,030 ± 381 | 0.5 | 73.3 |
| RTI-102 | 474 | 1928 | 43,400 | 4.06 | 91.5 |
| RTI-304 | 15 ± 1.2 | 7.1 ± 0.71 | 2,800 ± 300 | 0.5 | 186.6 |
| RTI-88 | 1.35 ± 0.11 | 120 ± 4 | 1,329 ± 124 | 88.9 | 984.0 |
| 83a* ‡ | 1.20 ± 0.29 | 48.7 ± 8.4 | 10,000.0 | 40.6 | 8,333.3 |
| RTI-143 | 4.06 ± 0.22 | 404 ± 56 | 40,270 ± 180 | 99.5 | 9,919.0 |
| C3β*-Ph-para=iodo, C2β-R=CO2-i-Pr, N8=CH2CH2CH2F | |||||
| ‡Compound code for phenyltropane in accord with Singh's "Chemistry, Design & SAR of cocaine antagonists" paper nomenclature, of no relation to RTI naming convention despite similarity to namesake of drug on topic. | |||||
| :: |
Such drugs are speculated to be useful as potential antidepressants, but few examples have been reported in the literature as yet. However, while RTI-83 has been used for binding studies to model the monoamine transporter proteins, its pharmacology in vivo has not been studied in detail.
References
References
- (September 1996). "Synthesis and transporter binding properties of 3 beta-(4'-alkyl-, 4'-alkenyl-, and 4'-alkynylphenyl)nortropane-2 beta-carboxylic acid methyl esters: serotonin transporter selective analogs". Journal of Medicinal Chemistry.
- (March 2000). "Chemistry, design, and structure-activity relationship of cocaine antagonists". Chemical Reviews.
- (2010). "Chem ''Inform'' Abstract: Chemistry, Design, and Structure-Activity Relationship of Cocaine Antagonists". ChemInform.
- (February 2004). "Distinct molecular recognition of psychostimulants by human and Drosophila serotonin transporters". The Journal of Pharmacology and Experimental Therapeutics.
::callout[type=info title="Wikipedia Source"] This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page. ::