RTI-51

(–)-2β-Carbomethoxy-3β-(4-bromophenyl)tropane (RTI-4229-51, bromopane) is a semi-synthetic alkaloid in the phenyltropane group of psychostimulant compounds. First publicized in the 1990s, it has not been used enough to have gained a fully established profile. RTI-51 can be expected to have properties lying somewhere in between RTI-31 and RTI-55. Importantly it has a ratio of monoamine reuptake inhibition of D > S > N (1.8:10.6:37.4nM respectively) which is an unusual balance of effects not produced by other commonly used compounds (although RTI-121 is similar, but more DAT selective).[1] It has been used in its 76Br radiolabelled form to map the distribution of dopamine transporters in the brain.[2]

Comparison of halogens
HalogenAtomic №Atomic WeightENBond Length
Fluorine919.04.0
Chlorine1735.53.2
Bromine3579.93.0
Iodine531272.7
RTI-51
Identifiers
CAS Number
PubChem CID
Chemical and physical data
FormulaC16H20BrNO2
Molar mass338.240 g/mol g·mol−1
3D model (JSmol)
 NY (what is this?)  (verify)

Modern research seems to confirm the above hypothesis.[3] However, earlier work produced more scattered results.[4] Based upon what is obvious from the table, RTI-31, RTI-51, and RTI-55 are all similarly potent TRIs.[5][6]

MAT IC50 (and Ki) for simple phenyltropanes with 1R,2S,3S stereochemistry.[7]
Compound[3H]CFT[3H]DA[3H]Nisoxetine[3H]NE[3H]Paroxetine[3H]5-HT
Cocaine[8]89.1275 cf. 2413300 (1990)119 cf. 1611050 (45)177 cf. 112
WIN 35,065-22349.8920 (550)37.21960 (178)173
WIN 35,42813.923.0835 (503)38.6692 (63)101
RTI-311.13.6837 (22)5.8644.5 (4.0)5.00
RTI-113[9]1.985.252,9262422,340391
RTI-511.7?37.4 (23)?10.6 (0.96)?
RTI-551.31.9636 (22)7.514.21 (0.38)1.74
RTI-321.77.0260 (36)8.42240 (23)19.4

Data in Above table from rats brains (1995). More recent work has advocated using cloned human transporter/s.

See also

References
  1. 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.
  2. Loch C, Müller L, Ottaviani M, Halldin C, Farde L, Maziere B. Synthesis of 2β-carbomethoxy-3β-(4-[76Br]bromophenyl)tropane ([76Br]β-CBT), a PET tracer for in vivo imaging of the dopamine uptake sites. Journal of labelled compounds & radiopharmaceuticals. 1995; 36(4):385-392.
  3. Wee, S.; Carroll, F.; Woolverton, W. (2006). "A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants". Neuropsychopharmacology. 31 (2): 351–362. doi:10.1038/sj.npp.1300795. PMID 15957006.
  4. Stathis, M.; Scheffel, U.; Lever, S. Z.; Boja, J. W.; Carroll, M. J.; Kuhar, F. I. (1995). "Rate of binding of various inhibitors at the dopamine transporter in vivo" (Submitted manuscript). Psychopharmacology. 119 (4): 376–384. doi:10.1007/BF02245852. PMID 7480516.
  5. Kimmel, HL; Carroll; Kuhar (2001). "Locomotor stimulant effects of novel phenyltropanes in the mouse". Drug and Alcohol Dependence. 65 (1): 25–36. doi:10.1016/S0376-8716(01)00144-2. PMID 11714587.
  6. Kuhar, M.; Carroll, F.; Bharat, N.; Landry, D. (2001). "Anticocaine catalytic antibodies have no affinity for RTI compounds: implications for treatment". Synapse. 41 (2): 176–178. doi:10.1002/syn.1072. PMID 11400184.
  7. Carroll, F. I.; Kotian, P.; Dehghani, A.; Gray, J. L.; Kuzemko, M. A.; Parham, K. A.; Abraham, P.; Lewin, A. H.; Boja, J. W.; Kuhar, M. J. (1995). "Cocaine and 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid ester and amide analogues. New high-affinity and selective compounds for the dopamine transporter". Journal of Medicinal Chemistry. 38 (2): 379–388. doi:10.1021/jm00002a020. PMID 7830281.
  8. Kozikowski, A.; Johnson, K.; Deschaux, O.; Bandyopadhyay, B.; Araldi, G.; Carmona, G.; Munzar, P.; Smith, M.; Balster, R. (2003). "Mixed cocaine agonist/antagonist properties of (+)-methyl 4beta-(4-chlorophenyl)-1-methylpiperidine-3alpha-carboxylate, a piperidine-based analog of cocaine". The Journal of Pharmacology and Experimental Therapeutics. 305 (1): 143–150. doi:10.1124/jpet.102.046318. PMID 12649362.
  9. Damaj, M. I.; Slemmer, J. E.; Carroll, F. I.; Martin, B. R. (1999). "Pharmacological characterization of nicotine's interaction with cocaine and cocaine analogs". The Journal of Pharmacology and Experimental Therapeutics. 289 (3): 1229–1236. PMID 10336510.
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