WIN 35,428 (β-CFT,(–)-2-β-Carbomethoxy-3-β-(4-fluorophenyl)tropane) is astimulant drug used in scientific research. CFT is aphenyltropane baseddopamine reuptake inhibitor and is structurally derived fromcocaine. It is around 3-10x more potent than cocaine and lasts around 7 times longer based on animal studies. While thenaphthalenedisulfonate salt is the most commonly used form in scientific research due to its highsolubility in water, the free base andhydrochloride salts are known compounds and can also be produced. The tartrate is another salt form that is reported.[1]
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 theDAT, although the drug also has someSERT affinity.
Radiolabelled forms of CFT have been used in humans and animals to map the distribution ofdopamine transporters in thebrain. CFT was found to be particularly useful for this application as a normal fluorine atom can be substituted with the radioactive isotope18F which is widely used inPositron emission tomography. Another radioisotope-substitutedanalog [11C]WIN 35,428 (where the carbon atom of either the N-methyl group, or themethyl from the 2-carbomethoxy group of CFT, has been replaced with11C) 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 reactingmethylecgonidine with parafluorophenylmagnesium bromide, and also avoids the requirement for a licence to work with the restricted precursorecgonine.
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 forcocaine, in a similar manner to howmethadone is used as a substitute foropiates in treating addiction.
In August 2010, some media sources claimed that thedesigner drugIvory Wave contained WIN 35428. However, these reports at the time were poorly researched and sensationalized: the use of the pseudonym 'meow meow' (forMephedrone) appears to have originated in the UK media.[3] Samples of Ivory Wave were later found to containMDPV,[4] and the careless and exploitative nature of reporting regarding new psychoactive compounds in this fashion not only served to raise awareness that such compounds were for sale and available to the public-at-large, but posed a significant risk to public health in its own right due to misleading or incorrect information.
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]
^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.PMID4747968.S2CID8105834.
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.PMID530372.S2CID31564203.
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.PMID6106874.
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.PMID1763097.S2CID53272758.
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.PMID2033595.S2CID22777518.
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.doi:10.1016/S0022-3565(25)11425-0.PMID1545384.
Singh S (March 2000). "Chemistry, design, and structure-activity relationship of cocaine antagonists".Chemical Reviews.100 (3):925–1024.doi:10.1021/cr9700538.PMID11749256.S2CID36764655.
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.PMID16478825.S2CID28919339.
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.PMID2362282.
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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