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{{Short description|Chemical compound}}
{{Drugbox
{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 413466418
| verifiedrevid = 413466418
| IUPAC_name = Methyl (1''R'',2''S'',3''S'',5''S'')-3-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
| IUPAC_name = Methyl (1''R'',2''S'',3''S'',5''S'')-3-(4-fluorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
| image = Phenyltropane 11b - WIN 35428.svg
| image = Phenyltropane 11b - WIN 35428.svg
<!--Clinical data-->
| tradename =
<!--Clinical data-->| tradename =
| legal_US = Schedule II
| legal_status =
<!--Identifiers-->
| legal_status = <!--Identifiers-->
| IUPHAR_ligand = 4606
| IUPHAR_ligand = 4606
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 50370-56-4
| CAS_number = 50370-56-4
| CAS_supplemental = <br>77210-32-3
| CAS_supplemental = <br>77210-32-3
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 8ZT6KJ947T
| UNII = 8ZT6KJ947T
| PubChem = 105056
| PubChem = 105056
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 541252
| ChEMBL = 541252
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 94788
| ChemSpiderID = 94788
<!--Chemical data-->
<!--Chemical data-->
| C=16 | H=20 | F=1 | N=1 | O=2
| C = 16
| H = 20
| molecular_weight = 277.33 g/mol (free base); 565.55 g/mol (anhydrous naphthalenedisulfonate)
| F = 1
⚫
| SMILES = CN1[C@H]2CC[C@@H]1[C@H]([C@H](C2)C3=CC=C(C=C3)F)C(=O)OC
| N = 1
⚫
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| O = 2
⚫
| StdInChI = 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
⚫
| SMILES = CN1[C@H]2CC[C@@H]1[C@H]([C@H](C2)C3=CC=C(C=C3)F)C(=O)OC
⚫
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
⚫
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
⚫
| StdInChIKey = QUSLQENMLDRCTO-YJNKXOJESA-N
⚫
| StdInChI = 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
⚫
| synonyms = CFT, WIN 35,428
⚫
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
⚫
| melting_point = 202
⚫
| StdInChIKey = QUSLQENMLDRCTO-YJNKXOJESA-N
⚫
| melting_high = 204
⚫
| synonyms = CFT, WIN 35,428
⚫
| specific_rotation = -62.5°
⚫
| melting_point = 202
⚫
| melting_high = 204
⚫
| specific_rotation = -62.5°
}}
}}


'''(–)-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 | 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 }}</ref>
'''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 [[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 | 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 = 351–362 | date = February 2006 | pmid = 15957006 | doi = 10.1038/sj.npp.1300795 | doi-access = free }}</ref>


== Uses ==
== Uses ==
CFT was first reported by Clarke and co-workers in 1973.<ref name=Clarke>{{cite journal | vauthors = Clarke RL, Daum SJ, Gambino AJ, Aceto MD, Pearl J, Levitt M, Cumiskey WR, Bogado EF | display-authors = 6 | 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 | date = November 1973 | pmid = 4747968 | doi = 10.1021/jm00269a600 | url = https://semanticscholar.org/paper/9272dea14c3ee1a95bacafc5d962ffd034c3c16c }}</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.
CFT was first reported by Clarke and co-workers in 1973.<ref name=Clarke>{{cite journal | vauthors = Clarke RL, Daum SJ, Gambino AJ, Aceto MD, Pearl J, Levitt M, Cumiskey WR, Bogado EF | display-authors = 6 | 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 = 1260–1267 | date = November 1973 | pmid = 4747968 | doi = 10.1021/jm00269a600 | s2cid = 8105834 }}</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|<sup>18</sup>F]] which is widely used in [[Positron emission tomography]]. Another radioisotope-substituted [[Structural analog|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 <sup>11</sup>C) 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]].
[[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|<sup>18</sup>F]] which is widely used in [[Positron emission tomography]]. Another radioisotope-substituted [[Structural analog|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 <sup>11</sup>C) 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]].
Line 46: Line 49:
== Street drug ==
== 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 |access-date=2010-08-23}}</ref> However, samples of Ivory Wave have been found to contain [[MDPV]],<ref>{{cite news| first1 = Sam | last1 = Jones | first2 = Mike | last2 = Power | name-list-format = vanc |url= https://www.theguardian.com/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|access-date=2010-08-23 | location=London}}</ref> so the legitimacy of these claims remains unclear.
In August 2010, some media sources claimed that the [[designer drug]] [[Ivory Wave]] contained WIN 35428.<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 |access-date=2010-08-23}}</ref> However, samples of Ivory Wave have been found to contain [[MDPV]],<ref>{{cite news| vauthors = Jones S, Power M |url= https://www.theguardian.com/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|access-date=2010-08-23 | location=London}}</ref> so the legitimacy of these claims remains unclear.


== Legal status ==
== Legal status ==


CFT is not specifically scheduled in the United States,<ref>{{cite web|url=http://www.justice.gov/dea/pubs/scheduling.html |title=DEA, Drug Scheduling |date= |access-date=2011-04-07}}</ref> though it is considered by chemical supply companies and perhaps law enforcement to be covered under the [[Federal Analog Act]] as a Schedule II due to its close similarity in structure and function to the schedule II drug [[cocaine]].<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) |date= |access-date=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= |access-date=2010-08-23}}</ref>
CFT is not specifically scheduled in the United States,<ref>{{cite web |url=https://www.justice.gov/dea/pubs/scheduling.html |title=DEA, Drug Scheduling |access-date=2011-04-07 |archive-date=2013-06-29 |archive-url=https://web.archive.org/web/20130629153729/http://www.justice.gov/dea/pubs/scheduling.html |url-status=dead }}</ref> though it meets the statutory definition of an ecgonine derivative. Consequently, it is a Schedule II drug.<ref>{{Cite web |title=21 USC 812: Schedules of controlled substances |url=https://uscode.house.gov/view.xhtml?req=38&f=treesort&num=5465 |access-date=2023-07-18 |website=uscode.house.gov}}</ref>


== Toxicity ==
== Toxicity ==


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 | vauthors = Carroll FI, Runyon SP, Abraham P, Navarro H, Kuhar MJ, Pollard GT, Howard 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 | date = December 2004 | pmid = 15566309 | doi = 10.1021/jm0401311 | url = https://semanticscholar.org/paper/fcfbda07d9ebd472e1f8a5757be7c8641adf74f1 }}</ref>
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 | vauthors = Carroll FI, Runyon SP, Abraham P, Navarro H, Kuhar MJ, Pollard GT, Howard 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 = 6401–6409 | date = December 2004 | pmid = 15566309 | doi = 10.1021/jm0401311 | s2cid = 26612669 }}</ref>


== See also ==
== See also ==
Line 65: Line 68:


== Further reading ==
== Further reading ==
{{refbegin}}
{{refbegin|30em}}
* {{cite journal | vauthors = D'Mello GD, Goldberg DM, Goldberg SR, Stolerman IP | title = Conditioned taste aversion and operant behaviour in rats: effects of cocaine and a cocaine analogue (WIN 35,428) | journal = Neuropharmacology | volume = 18 | issue = 12 | pages = 1009–10 | date = December 1979 | pmid = 530372 | doi = 10.1016/0028-3908(79)90167-9 }}
* {{cite journal | vauthors = D'Mello GD, Goldberg DM, Goldberg SR, Stolerman IP | title = Conditioned taste aversion and operant behaviour in rats: effects of cocaine and a cocaine analogue (WIN 35,428) | journal = Neuropharmacology | volume = 18 | issue = 12 | pages = 1009–1010 | date = December 1979 | pmid = 530372 | doi = 10.1016/0028-3908(79)90167-9 | s2cid = 31564203 }}
* {{cite journal | vauthors = Reith ME, Sershen H, Lajtha A | title = Saturable (3H)cocaine binding in central nervous system of mouse | journal = Life Sciences | volume = 27 | issue = 12 | pages = 1055–62 | date = September 1980 | pmid = 6106874 | doi = 10.1016/0024-3205(80)90029-6 }}
* {{cite journal | vauthors = Reith ME, Sershen H, Lajtha A | title = Saturable (3H)cocaine binding in central nervous system of mouse | journal = Life Sciences | volume = 27 | issue = 12 | pages = 1055–1062 | date = September 1980 | pmid = 6106874 | doi = 10.1016/0024-3205(80)90029-6 }}
* {{cite journal | last1 = Spealman | first1 = RD | last2 = Bergman | first2 = J | last3 = Madras | first3 = BK | date = Aug 1991 | title = Self-administration of the high-affinity cocaine analog 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane | url = | journal = Pharmacology Biochemistry and Behavior | volume = 39 | issue = 4| pages = 1011–3 | doi=10.1016/0091-3057(91)90067-c| pmid = 1763097 }}
* {{cite journal | vauthors = Spealman RD, Bergman J, Madras BK | title = Self-administration of the high-affinity cocaine analog 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane | journal = Pharmacology, Biochemistry, and Behavior | volume = 39 | issue = 4 | pages = 1011–1013 | date = August 1991 | pmid = 1763097 | doi = 10.1016/0091-3057(91)90067-c | s2cid = 53272758 }}
* {{cite journal | vauthors = Milius RA, Saha JK, Madras BK, Neumeyer JL | title = Synthesis and receptor binding of N-substituted tropane derivatives. High-affinity ligands for the cocaine receptor | journal = Journal of Medicinal Chemistry | volume = 34 | issue = 5 | pages = 1728–31 | date = May 1991 | pmid = 2033595 | doi = 10.1021/jm00109a029 | url = https://semanticscholar.org/paper/0ce67d6c8a4df7f81d53c86d2d44904c11fc6084 }}
* {{cite journal | vauthors = Milius RA, Saha JK, Madras BK, Neumeyer JL | title = Synthesis and receptor binding of N-substituted tropane derivatives. High-affinity ligands for the cocaine receptor | journal = Journal of Medicinal Chemistry | volume = 34 | issue = 5 | pages = 1728–1731 | date = May 1991 | pmid = 2033595 | doi = 10.1021/jm00109a029 | s2cid = 22777518 }}
* {{cite journal | last1 = Cline | first1 = EJ | last2 = Scheffel | first2 = U | last3 = Boja | first3 = JW | last4 = Carroll | first4 = FI | last5 = Katz | first5 = JL | last6 = Kuhar | first6 = MJ | date = Mar 1992 | title = Behavioral effects of novel cocaine analogs: a comparison with in vivo receptor binding potency | url = | journal = Journal of Pharmacology and Experimental Therapeutics | volume = 260 | issue = 3| pages = 1174–9 }}
* {{cite journal | vauthors = Cline EJ, Scheffel U, Boja JW, Carroll FI, Katz JL, Kuhar MJ | title = Behavioral effects of novel cocaine analogs: a comparison with in vivo receptor binding potency | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 260 | issue = 3 | pages = 1174–1179 | date = March 1992 | pmid = 1545384 }}
* {{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 | url = https://semanticscholar.org/paper/c73b8f1f14d0971c0ff8751f48f7dff197c58ff8 }}
* {{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 | s2cid = 36764655 }}
* {{cite journal | vauthors = Li SM, Campbell BL, Katz JL | title = Interactions of cocaine with dopamine uptake inhibitors or dopamine releasers in rats discriminating cocaine | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 317 | issue = 3 | pages = 1088–96 | date = June 2006 | pmid = 16478825 | doi = 10.1124/jpet.105.100594 | url = https://semanticscholar.org/paper/d014d66d34c723c4c4acde402def9b37c7444676 }}
* {{cite journal | vauthors = Li SM, Campbell BL, Katz JL | title = Interactions of cocaine with dopamine uptake inhibitors or dopamine releasers in rats discriminating cocaine | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 317 | issue = 3 | pages = 1088–1096 | date = June 2006 | pmid = 16478825 | doi = 10.1124/jpet.105.100594 | s2cid = 28919339 }}
* {{cite journal | vauthors = Kline RH, Wright J, Fox KM, Eldefrawi ME | title = Synthesis of 3-arylecgonine analogues as inhibitors of cocaine binding and dopamine uptake | journal = Journal of Medicinal Chemistry | volume = 33 | issue = 7 | pages = 2024–7 | date = July 1990 | pmid = 2362282 | doi = 10.1021/jm00169a036 }}
* {{cite journal | vauthors = Kline RH, Wright J, Fox KM, Eldefrawi ME | title = Synthesis of 3-arylecgonine analogues as inhibitors of cocaine binding and dopamine uptake | journal = Journal of Medicinal Chemistry | volume = 33 | issue = 7 | pages = 2024–2027 | date = July 1990 | pmid = 2362282 | doi = 10.1021/jm00169a036 }}
* {{cite journal | vauthors = Xu L, Trudell ML | title = Stereoselective synthesis of 2β‐carbomethoxy‐3β‐phenyltropane derivatives. Enhanced stereoselectivity observed for the conjugate addition reaction of phenylmagnesium bromide derivatives with anhydro dichloromethane. | journal = Journal of Heterocyclic Chemistry | date = November 1996 | volume = 33 | issue = 6 | pages = 2037–9 | doi = 10.1002/jhet.5570330676 }}
* {{cite journal | vauthors = Xu L, Trudell ML | title = Stereoselective synthesis of 2β-carbomethoxy-3β-phenyltropane derivatives. Enhanced stereoselectivity observed for the conjugate addition reaction of phenylmagnesium bromide derivatives with anhydro dichloromethane. | journal = Journal of Heterocyclic Chemistry | date = November 1996 | volume = 33 | issue = 6 | pages = 2037–9 | doi = 10.1002/jhet.5570330676 }}
{{refend}}
{{refend}}


Latest revision as of 14:38, 10 June 2024

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)

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]

Uses

[edit]

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

[edit]

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.

[edit]

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

[edit]

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

[edit]

References

[edit]
  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

[edit]
  • 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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