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CAS Number
PubChem CID
Chemical and physical data
Formula C18H25NO2
Molar mass 287.396 g/mol
3D model (Jmol)

(–)-2β-Carbomethoxy-3β-(4-ethylphenyl)tropane (RTI-4229-83) 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

cis-propenyl analogue (RTI-304)

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 (3.09nM @ DAT & 1,960nM @ 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 & SERT being 88)

Binding comparison between phenyltropanes with high NET/DAT selectivity ratios
Compound DAT

[3H]WIN 35428









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[a] 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,[4] its pharmacology in vivo has not been studied in detail.

See also[edit]

External links[edit]


  1. ^ Blough BE, Abraham P, Lewin AH, Kuhar MJ, Boja JW, Carroll FI. 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. 1996 Sep 27;39(20):4027-35. PMID 8831768
  2. ^ Singh S (March 2000). "Chemistry, design, and structure-activity relationship of cocaine antagonists". Chemical Reviews. 100 (3): 925–1024. doi:10.1021/cr9700538. PMID 11749256. 
  3. ^ Chemistry, Design, and Structure-Activity Relationship of Cocaine Antagonists. Satendra Singh et al. Chem. Rev. 2000, 100. 925-1024. PubMed; Chemical Reviews (Impact Factor: 45.66). 04/2000; 100(3):925-1024 American Chemical Society; 2000 ISSN 0009-2665 ChemInform; May, 16th 2000, Volume 31, Issue 20, doi:10.1002/chin.200020238. Mirror hotlink.
  4. ^ Roman DL, Saldaña SN, Nichols DE, Carroll FI, Barker EL. Distinct molecular recognition of psychostimulants by human and Drosophila serotonin transporters. Journal of Pharmacology and Experimental Therapeutics. 2004 Feb;308(2):679-87. PMID 14593087