WIN-35428: Difference between revisions

{{Drugbox|

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

| image = WIN 35428 structural formula.png

| CAS_number= 50370-56-4

| CAS_supplemental = <br>77210-32-3

| ATC_prefix=

| ATC_suffix=

| PubChem= 105056

| DrugBank=

| chemical_formula = C₁₆H₂₀FNO₂·C₁₀H₈S₂O₆

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

| molecular_weight = 277.33 g/mol (free base); 565.55 (anhydrous naphthalenedisulfonate)

| smiles = CN1[C@H]2CC[C@@H]1[C@H]([C@H](C2)C3=CC=C(C=C3)F)C(=O)OC

| synonyms = CFT, WIN 35,428

| melting_point = 202

| melting_high = 204

| specific_rotation = -62.5°

| bioavailability=

| metabolism =

| elimination_half-life=

| excretion =

| pregnancy_category =

| legal_status = Schedule II (US)

| routes_of_administration=

'''(–)-2-β-Carbomethoxy-3-β-(4-fluorophenyl)tropane''' ('''β-CFT''', '''WIN 35,428''') 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 [[Armstrong's acid|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.<ref name=Wee>{{cite journal | last1 = Wee | first1 = S | last2 = Carroll | first2 = FI | last3 = Woolverton | first3 = WL | title = A reduced rate of in vivo dopamine transporter binding is associated with lower relative reinforcing efficacy of stimulants | url = http://www.nature.com/npp/journal/v31/n2/full/1300795a.html | journal = Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology | volume = 31 | issue = 2 | pages = 351–62 | year = 2006 | pmid = 15957006 | doi = 10.1038/sj.npp.1300795 }}</ref>

CFT was first reported by Clarke and co-workers in 1973.<ref name=Clarke>{{cite journal | last1 = Clarke | first1 = RL | last2 = Daum | first2 = SJ | last3 = Gambino | first3 = AJ | last4 = Aceto | first4 = MD | last5 = Pearl | first5 = J | last6 = Levitt | first6 = M | last7 = Cumiskey | first7 = WR | last8 = Bogado | first8 = EF | title = Compounds affecting the central nervous system. 4. 3 Beta-phenyltropane-2-carboxylic esters and analogs | journal = Journal of medicinal chemistry | volume = 16 | issue = 11 | pages = 1260–7 | year = 1973 | pmid = 4747968 | doi=10.1021/jm00269a600}}</ref> This drug is known to function as a "positive reinforcer" (although it is less likely to be self-administered by rhesus monkeys than cocaine).<ref name=Wee/> Tritiated CFT is frequently used to map binding of novel ligands to the [[Dopamine active transporter|DAT]], although the drug also has some [[Serotonin transporter|SERT]] affinity.

[[Isotopic labeling|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 [[Fluorine-18|¹⁸F]] which is widely used in [[Positron emission tomography]]. Another radioisotope-substituted [[analogue]] [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]].

== Street Drug ==

In August 2010, some media sources claimed that the [[designer drug]], [[Ivory Wave]] contained WIN 35,428.<ref name="Metro.co.uk">{{cite web|url=http://www.metro.co.uk/news/838315-ivory-wave-the-new-meow-meow |title=Ivory Wave: The new meow meow? |publisher=Metro.co.uk |date=2010-08-17 |accessdate=2010-08-23}}</ref> However, samples of Ivory Wave have been found to contain [[MDPV]],<ref>{{cite news|author=Sam Jones and Mike Power |url=http://www.guardian.co.uk/society/2010/aug/17/ivory-wave-drug-alleged-death |title=Ivory Wave drug implicated in death of 24-year-old man &#124; Society &#124; guardian.co.uk |publisher=Guardian |date= 2010-08-17|accessdate=2010-08-23 | location=London}}</ref> so the legitimacy of these claims remains unclear.

== Legal Status ==

CFT is illegal in the [[USA]] (Schedule II)<ref>{{cite web|url=http://www.visn20.med.va.gov/portland/research/pdf-documents/csi_research_policy.pdf |title=Controlled Substances in Research Policy (Portland VA Medical Center) |format=PDF |date= |accessdate=2010-08-23}}</ref><ref name="sigma">{{cite web|url=http://www.sigmaaldrich.com/catalog/search/ProductDetail?ProdNo=C124&Brand=SIGMA |title=C124 β-CFT naphthalenedisulfonate monohydrate solid |publisher=Sigmaaldrich.com |date= |accessdate=2010-08-23}}</ref> and [[Germany]] (Kontrollierte Droge).<ref name="sigma"/> Its legal status in other countries is unclear.

Administering 100&nbsp;mg/kg of CFT to rats only resulted in convulsions being reported, whereas [[RTI-55|CIT]] had the ability to cause death at this dose.<ref name=Navarro>{{cite journal | last1 = Carroll | first1 = FI | last2 = Runyon | first2 = SP | last3 = Abraham | first3 = P | last4 = Navarro | first4 = H | last5 = Kuhar | first5 = MJ | last6 = Pollard | first6 = GT | last7 = Howard | first7 = JL | title = Monoamine transporter binding, locomotor activity, and drug discrimination properties of 3-(4-substituted-phenyl)tropane-2-carboxylic acid methyl ester isomers | journal = Journal of medicinal chemistry | volume = 47 | issue = 25 | pages = 6401–9 | year = 2004 | pmid = 15566309 | doi = 10.1021/jm0401311 }}</ref>

==See also==

==References==

==References==

*D'Mello GD, Goldberg DM, Goldberg SR, Stolerman IP. Conditioned taste aversion and operant behaviour in rats: effects of cocaine and a cocaine analogue (WIN 35,428). ''Neuropharmacology''. 1979 Dec;18(12):1009-10.

*Reith, MEA., Sershen H, Lajtha A. Saturable (3H)cocaine binding in central nervous system of mouse. ''Life Sciences''. 1980 Sep 22;27(12):1055-62.

*Spealman RD, Bergman J, Madras BK. Self-administration of the high-affinity cocaine analog 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane. ''Pharmacology Biochemistry and Behaviour''. 1991 Aug;39(4):1011-3.

*Milius RA, Saha JK, Madras BK, Neumeyer JL. Synthesis and Receptor Binding of N-Substituted Tropane Derivatives. High- Affinity Ligands for the Cocaine Receptor. ''Journal of Medicinal Chemistry''. 1991,34, 1728–1731

*Cline EJ, Scheffel U, Boja JW, Carroll FI, Katz JL, Kuhar MJ. Behavioral effects of novel cocaine analogs: a comparison with in vivo receptor binding potency. ''Journal of Pharmacology and Experimental Therapeutics''. 1992 Mar;260(3):1174-9.

*Singh S. Chemistry, Design, and Structure-Activity Relationship of Cocaine Antagonists. ''Chemistry Reviews'', 2000. 100(3): 925-1024

*Li SM, Campbell BL, Katz JL. Interactions of cocaine with dopamine uptake inhibitors or dopamine releasers in rats discriminating cocaine. ''Journal of Pharmacology and Experimental Therapeutics''. 2006 Jun;317(3):1088-96.

*Richard H. Kline, Jr., Jeremy Wright, Kristine M. Fox, and Mohyee E. Eldefrawi. Synthesis of 3- Arylecgonine Analogues as Inhibitors of Cocaine Binding and Dopamine Uptake. ''Journal of Medicinal Chemistry'' 1990, (33): 2024-2027.

*Xu L, Trudell ML. ''Journal of Heterocyclic Chemistry''. 1996; 33: 2037.

{{Phenyltropanes}}

{{Dopaminergics}}

[[Category:Organofluorides]]