RTI-83
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| Clinical data | |
|---|---|
| Other names | RTI-4229-83 |
| Identifiers | |
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JSmol) | |
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RTI-83 ((–)-2β-carbomethoxy-3β-(4-ethylphenyl)tropane) is a
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.[1][2] 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).
| Compound | DAT
[3H]WIN-35428 |
5-HTT
[3H]Paroxetine |
NET
[3H]Nisoxetine |
Selectivity
5-HTT/DAT |
Selectivity
NET/DAT | |||
|---|---|---|---|---|---|---|---|---|
| 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.[3] | ||||||||
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,[4] its pharmacology in vivo has not been studied in detail.
See also
References
External links
- Jin C, Navarro HA, Carroll FI (December 2008). "Development of 3-phenyltropane analogues with high affinity for the dopamine and serotonin transporters and low affinity for the norepinephrine transporter". Journal of Medicinal Chemistry. 51 (24): 8048–56. PMID 19053748.