RTI-51

{{Short description|Chemical compound}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 449586292

| IUPAC_name = methyl (1R,2S,3S,5S)-3-(4-bromophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate

| image = RTI-51.png

| tradename =

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 135367-08-7

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = C3MV2GV7R7

| ATC_prefix =

| ATC_suffix =

| PubChem = 22595194

| C=16 | H=20 | Br=1 | N=1 | O=2

| smiles = Brc1ccc(cc1)[C@H]2C[C@@H]3N(C)[C@H]([C@H]2C(=O)OC)CC3

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI=1S/C16H20BrNO2/c1-18-12-7-8-14(18)15(16(19)20-2)13(9-12)10-3-5-11(17)6-4-10/h3-6,12-15H,7-9H2,1-2H3/t12-,13-,14+,15+/m1/s1

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = HNVGNUVAMRLMSG-KBXIAJHMSA-N

}}

(–)-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).{{cite journal | vauthors = Singh S | title = Chemistry, design, and structure-activity relationship of cocaine antagonists | journal = Chemical Reviews | volume = 100 | issue = 3 | pages = 925–1024 | date = March 2000 | pmid = 11749256 | doi = 10.1021/cr9700538 }} It has been used in its {{nobr|⁷⁶Br}} radiolabelled form to map the distribution of dopamine transporters in the brain.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.

Modern research seems to confirm the above hypothesis.{{cite journal | vauthors = Wee S, Carroll FI, Woolverton WL | title = A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants | journal = Neuropsychopharmacology | volume = 31 | issue = 2 | pages = 351–62 | date = February 2006 | pmid = 15957006 | doi = 10.1038/sj.npp.1300795 | s2cid = 7224342 | doi-access = free }} However, earlier work produced more scattered results.{{cite journal | vauthors = Stathis M, Scheffel U, Lever SZ, Boja JW, Carroll FI, Kuhar MJ | title = Rate of binding of various inhibitors at the dopamine transporter in vivo | journal = Psychopharmacology | volume = 119 | issue = 4 | pages = 376–84 | date = June 1995 | pmid = 7480516 | doi = 10.1007/BF02245852 | s2cid = 20022021 | url = https://zenodo.org/record/1232524 }} Based upon what is obvious from the table, RTI-31, RTI-51, and RTI-55 are all similarly potent TRIs.{{cite journal | vauthors = Kimmel HL, Carroll FI, Kuhar MJ | title = Locomotor stimulant effects of novel phenyltropanes in the mouse | journal = Drug and Alcohol Dependence | volume = 65 | issue = 1 | pages = 25–36 | date = December 2001 | pmid = 11714587 | doi = 10.1016/S0376-8716(01)00144-2 }}{{cite journal | vauthors = Kuhar MJ, Carroll FI, Bharat N, Landry DW | title = Anticocaine catalytic antibodies have no affinity for RTI compounds: implications for treatment | journal = Synapse | volume = 41 | issue = 2 | pages = 176–8 | date = August 2001 | pmid = 11400184 | doi = 10.1002/syn.1072 | s2cid = 11862673 }}

class="wikitable" |+MAT IC50 (and Ki) for simple phenyltropanes with 1R,2S,3S stereochemistry.{{cite journal | vauthors = Carroll FI, Kotian P, Dehghani A, Gray JL, Kuzemko MA, Parham KA, Abraham P, Lewin AH, Boja JW, Kuhar MJ | display-authors = 6 | title = 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 = Journal of Medicinal Chemistry | volume = 38 | issue = 2 | pages = 379–88 | date = January 1995 | pmid = 7830281 | doi = 10.1021/jm00002a020 }}
Compound	[3H]CFT	[3H]DA	[3H]Nisoxetine	[3H]NE	[3H]Paroxetine	[3H]5-HT
Cocaine{{cite journal | vauthors = Kozikowski AP, Johnson KM, Deschaux O, Bandyopadhyay BC, Araldi GL, Carmona G, Munzar P, Smith MP, Balster RL, Beardsley PM, Tella SR | display-authors = 6 | title = Mixed cocaine agonist/antagonist properties of (+)-methyl 4beta-(4-chlorophenyl)-1-methylpiperidine-3alpha-carboxylate, a piperidine-based analog of cocaine | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 305 | issue = 1 | pages = 143–50 | date = April 2003 | pmid = 12649362 | doi = 10.1124/jpet.102.046318 | s2cid = 29377097 }}	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{{cite journal | vauthors = Damaj MI, Slemmer JE, Carroll FI, Martin BR | title = Pharmacological characterization of nicotine's interaction with cocaine and cocaine analogs | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 289 | issue = 3 | pages = 1229–36 | date = June 1999 | pmid = 10336510 }}	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.