RTI-51 explained

(–)-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. It has a ratio of monoamine reuptake inhibition of dopamine > serotonin > norepinephrine (1.8:10.6:37.4 nM 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 radiolabelled form to map the distribution of dopamine transporters in the brain.^[2]

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 K_i) for simple phenyltropanes with 1R,2S,3S stereochemistry.^[7]

Compound	[<sup>3</sup>H]CFT	[<sup>3</sup>H]DA	[<sup>3</sup>H]Nisoxetine	[<sup>3</sup>H]NE	[<sup>3</sup>H]Paroxetine	[<sup>3</sup>H]5-HT
Cocaine^[8]	89.1	275 cf. 241	3300 (1990)	119 cf. 161	1050 (45)	177 cf. 112
WIN 35,065-2	23	49.8	920 (550)	37.2	1960 (178)	173
WIN 35,428	13.9	23.0	835 (503)	38.6	692 (63)	101
RTI-31	1.1	3.68	37 (22)	5.86	44.5 (4.0)	5.00
RTI-113^[9]	1.98	5.25	2,926	242	2,340	391
RTI-51	1.7	?	37.4 (23)	?	10.6 (0.96)	?
RTI-55	1.3	1.96	36 (22)	7.51	4.21 (0.38)	1.74
RTI-32	1.7	7.02	60 (36)	8.42	240 (23)	19.4

Data in above table is from rats brains (1995). More recent work has advocated using cloned human transporters.

See also

• List of cocaine analogues

Notes and References

1. Singh S . Chemistry, design, and structure-activity relationship of cocaine antagonists . Chemical Reviews . 100 . 3 . 925–1024 . March 2000 . 11749256 . 10.1021/cr9700538 .
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 FI, Woolverton WL . A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants . Neuropsychopharmacology . 31 . 2 . 351–62 . February 2006 . 15957006 . 10.1038/sj.npp.1300795 . 7224342 . free .
4. Stathis M, Scheffel U, Lever SZ, Boja JW, Carroll FI, Kuhar MJ . Rate of binding of various inhibitors at the dopamine transporter in vivo . Psychopharmacology . 119 . 4 . 376–84 . June 1995 . 7480516 . 10.1007/BF02245852 . 20022021 .
5. Kimmel HL, Carroll FI, Kuhar MJ . Locomotor stimulant effects of novel phenyltropanes in the mouse . Drug and Alcohol Dependence . 65 . 1 . 25–36 . December 2001 . 11714587 . 10.1016/S0376-8716(01)00144-2 .
6. Kuhar MJ, Carroll FI, Bharat N, Landry DW . Anticocaine catalytic antibodies have no affinity for RTI compounds: implications for treatment . Synapse . 41 . 2 . 176–8 . August 2001 . 11400184 . 10.1002/syn.1072 . 11862673 .
7. Carroll FI, Kotian P, Dehghani A, Gray JL, Kuzemko MA, Parham KA, Abraham P, Lewin AH, Boja JW, Kuhar MJ . 6 . 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 . 379–88 . January 1995 . 7830281 . 10.1021/jm00002a020 .
8. Kozikowski AP, Johnson KM, Deschaux O, Bandyopadhyay BC, Araldi GL, Carmona G, Munzar P, Smith MP, Balster RL, Beardsley PM, Tella SR . 6 . 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 . 143–50 . April 2003 . 12649362 . 10.1124/jpet.102.046318 . 29377097 .
9. Damaj MI, Slemmer JE, Carroll FI, Martin BR . Pharmacological characterization of nicotine's interaction with cocaine and cocaine analogs . The Journal of Pharmacology and Experimental Therapeutics . 289 . 3 . 1229–36 . June 1999 . 10336510 .