Wikipedia

WIN-35428

(Redirected from (-)-2-b-Carbomethoxy-3-b-(4-fluorophenyl)tropane naphthalenedisulfonate)

WIN 35,428 (β-CFT, (–)-2-β-Carbomethoxy-3-β-(4-fluorophenyl)tropane) is a stimulant drug used in scientific research. CFT is a phenyltropane based dopamine reuptake inhibitor and is structurally derived from cocaine. It is around 3-10x more potent than cocaine and lasts around 7 times longer based on animal studies. While the naphthalenedisulfonate salt is the most commonly used form in scientific research due to its high solubility in water, the free base and hydrochloride salts are known compounds and can also be produced. The tartrate is another salt form that is reported.[1]

WIN-35428
Clinical data
Other namesCFT, WIN 35,428
Legal status
Legal status
Identifiers
  • Methyl (1R,2S,3S,5S)-3-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.164.866 Edit this at Wikidata
Chemical and physical data
FormulaC16H20FNO2
Molar mass277.339 g·mol−1
3D model (JSmol)
Specific rotation-62.5°
Melting point202 to 204 °C (396 to 399 °F)
  • CN1[C@H]2CC[C@@H]1[C@H]([C@H](C2)C3=CC=C(C=C3)F)C(=O)OC
  • InChI=1S/C16H20FNO2/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-/m0/s1 ☒N
  • Key:QUSLQENMLDRCTO-YJNKXOJESA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Uses

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CFT was first reported by Clarke and co-workers in 1973.[2] This drug is known to function as a "positive reinforcer" (although it is less likely to be self-administered by rhesus monkeys than cocaine).[1] Tritiated CFT is frequently used to map binding of novel ligands to the DAT, although the drug also has some SERT affinity.

Radiolabelled forms of CFT have been used in humans and animals to map the distribution of dopamine transporters in the brain. CFT was found to be particularly useful for this application as a normal fluorine atom can be substituted with the radioactive isotope 18F which is widely used in Positron emission tomography. Another radioisotope-substituted analog [11C]WIN 35,428 (where the carbon atom of either the N-methyl group, or the methyl from the 2-carbomethoxy group of CFT, has been replaced with 11C) is now more commonly used for this application, as it is quicker and easier in practice to make radiolabelled CFT by methylating nor-CFT or 2-desmethyl-CFT than by reacting methylecgonidine with parafluorophenylmagnesium bromide, and also avoids the requirement for a licence to work with the restricted precursor ecgonine.

CFT is about as addictive as cocaine in animal studies, but is taken less often due to its longer duration of action. Potentially this could make it a suitable drug to be used as a substitute for cocaine, in a similar manner to how methadone is used as a substitute for opiates in treating addiction.

Street drug

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In August 2010, some media sources claimed that the designer drug Ivory Wave contained WIN 35428.[3] However, samples of Ivory Wave have been found to contain MDPV,[4] so the legitimacy of these claims remains unclear.

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CFT is not specifically scheduled in the United States,[5] though it meets the statutory definition of an ecgonine derivative. Consequently, it is a Schedule II drug.[6]

Toxicity

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Administering 100 mg/kg of CFT to rats only resulted in convulsions being reported, whereas CIT had the ability to cause death at this dose.[7]

See also

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References

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  1. ^ a b Wee S, Carroll FI, Woolverton WL (February 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.
  2. ^ Clarke RL, Daum SJ, Gambino AJ, Aceto MD, Pearl J, Levitt M, et al. (November 1973). "Compounds affecting the central nervous system. 4. 3 Beta-phenyltropane-2-carboxylic esters and analogs". Journal of Medicinal Chemistry. 16 (11): 1260–1267. doi:10.1021/jm00269a600. PMID 4747968. S2CID 8105834.
  3. ^ "Ivory Wave: The new meow meow?". Metro.co.uk. 2010-08-17. Retrieved 2010-08-23.
  4. ^ Jones S, Power M (2010-08-17). "Ivory Wave drug implicated in death of 24-year-old man | Society | guardian.co.uk". London: Guardian. Retrieved 2010-08-23.
  5. ^ "DEA, Drug Scheduling". Archived from the original on 2013-06-29. Retrieved 2011-04-07.
  6. ^ "21 USC 812: Schedules of controlled substances". uscode.house.gov. Retrieved 2023-07-18.
  7. ^ Carroll FI, Runyon SP, Abraham P, Navarro H, Kuhar MJ, Pollard GT, Howard JL (December 2004). "Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester isomers". Journal of Medicinal Chemistry. 47 (25): 6401–6409. doi:10.1021/jm0401311. PMID 15566309. S2CID 26612669.

Further reading

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  • D'Mello GD, Goldberg DM, Goldberg SR, Stolerman IP (December 1979). "Conditioned taste aversion and operant behaviour in rats: effects of cocaine and a cocaine analogue (WIN 35,428)". Neuropharmacology. 18 (12): 1009–1010. doi:10.1016/0028-3908(79)90167-9. PMID 530372. S2CID 31564203.
  • Reith ME, Sershen H, Lajtha A (September 1980). "Saturable (3H)cocaine binding in central nervous system of mouse". Life Sciences. 27 (12): 1055–1062. doi:10.1016/0024-3205(80)90029-6. PMID 6106874.
  • Spealman RD, Bergman J, Madras BK (August 1991). "Self-administration of the high-affinity cocaine analog 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane". Pharmacology, Biochemistry, and Behavior. 39 (4): 1011–1013. doi:10.1016/0091-3057(91)90067-c. PMID 1763097. S2CID 53272758.
  • Milius RA, Saha JK, Madras BK, Neumeyer JL (May 1991). "Synthesis and receptor binding of N-substituted tropane derivatives. High-affinity ligands for the cocaine receptor". Journal of Medicinal Chemistry. 34 (5): 1728–1731. doi:10.1021/jm00109a029. PMID 2033595. S2CID 22777518.
  • Cline EJ, Scheffel U, Boja JW, Carroll FI, Katz JL, Kuhar MJ (March 1992). "Behavioral effects of novel cocaine analogs: a comparison with in vivo receptor binding potency". The Journal of Pharmacology and Experimental Therapeutics. 260 (3): 1174–1179. PMID 1545384.
  • 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. S2CID 36764655.
  • Li SM, Campbell BL, Katz JL (June 2006). "Interactions of cocaine with dopamine uptake inhibitors or dopamine releasers in rats discriminating cocaine". The Journal of Pharmacology and Experimental Therapeutics. 317 (3): 1088–1096. doi:10.1124/jpet.105.100594. PMID 16478825. S2CID 28919339.
  • Kline RH, Wright J, Fox KM, Eldefrawi ME (July 1990). "Synthesis of 3-arylecgonine analogues as inhibitors of cocaine binding and dopamine uptake". Journal of Medicinal Chemistry. 33 (7): 2024–2027. doi:10.1021/jm00169a036. PMID 2362282.
  • Xu L, Trudell ML (November 1996). "Stereoselective synthesis of 2β-carbomethoxy-3β-phenyltropane derivatives. Enhanced stereoselectivity observed for the conjugate addition reaction of phenylmagnesium bromide derivatives with anhydro dichloromethane". Journal of Heterocyclic Chemistry. 33 (6): 2037–9. doi:10.1002/jhet.5570330676.
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