4F-MPH: Difference between revisions

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'''4-Fluoromethylphenidate''' (commonly known as '''4F-MPH''') is a novel synthetic [[psychoactive class::stimulant]] of the [[chemical class::phenidate]] class that produces long-lasting [[Euphoria|euphoriant]], and [[stimulant|stimulating]] effects when [[Routes of administration|administered]]. It is a closely related structural analog of the commonly prescribed ADHD drug [[methylphenidate]] (known by the brand-names ''Ritalin'' and ''Concerta'').

The two substances are believed to have very similar pharmacological mechanisms as [[monoamine]] [[reuptake inhibitors]] but have been reported to display distinctive [[subjective effects index|subjective effects]], with 4F-MPH being considered significantly more euphoric and recreational. Anecdotal reports suggest that it is considerably more potent with fewer uncomfortable side effects such as [[anxiety]], [[muscle spasms]] and [[compulsive redosing]].<ref>http://www.bluelight.org/vb/threads/770658-4-Fluoromethylphenidate-(4F-MPH)</ref> This perhaps owes to the fact that it has been shown to act as a higher efficiency [[dopamine]] reuptake inhibitor than the parent compound methylphenidate.<ref>Deutsch, H. M., Shi, Q., Gruszecka-Kowalik, E., & Schweri, M. M. ~~(1996~~). Synthesis and ~~pharmacology~~ of ~~potential cocaine antagonists~~. 2. ~~Structure-activity relationship studies~~ of ~~aromatic ring~~-~~substituted methylphenidate analogs. Journal of medicinal chemistry,~~ 39(6~~), 1201-1209.~~ https://~~www~~.~~doi~~.org/10.1021/jm950697c</ref><ref>Biochemical and behavioral characterization of novel methylphenidate analogs ~~(PubMed~~.~~gov~~ / ~~NCBI) | https://www~~.~~ncbi~~.~~nlm~~.~~nih.gov/pubmed/11961053~~</ref><ref>Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites ~~(PubMed~~.~~gov / NCBI) | https:~~/~~/www~~.~~ncbi~~.~~nlm~~.~~nih~~.~~gov/pubmed/15026075~~</ref><ref>Quantitative structure-activity relationship studies of threo-methylphenidate analogs ~~(PubMed~~.~~gov / NCBI) | https:/~~/~~www~~.~~ncbi~~.~~nlm~~.~~nih~~.~~gov/pubmed/20846865~~</ref><ref>Chemistry, Design, and Structure−Activity Relationship of Cocaine Antagonists | ~~http~~://pubs.acs.org/doi/~~abs~~/10.1021/cr9700538</ref>

The two substances are believed to have very similar pharmacological mechanisms as [[monoamine]] [[reuptake inhibitors]] but have been reported to display distinctive [[subjective effects index|subjective effects]], with 4F-MPH being considered significantly more euphoric and recreational. Anecdotal reports suggest that it is considerably more potent with fewer uncomfortable side effects such as [[anxiety]], [[muscle spasms]] and [[compulsive redosing]].<ref>http://www.bluelight.org/vb/threads/770658-4-Fluoromethylphenidate-(4F-MPH)</ref> This perhaps owes to the fact that it has been shown to act as a higher efficiency [[dopamine]] reuptake inhibitor than the parent compound methylphenidate.<ref>{{cite journal | vauthors=((Deutsch, H. M.)), ((Shi, Q.)), ((Gruszecka-Kowalik, E.)), ((Schweri, M. M.)) | journal=Journal of Medicinal Chemistry | title=Synthesis and Pharmacology of Potential Cocaine Antagonists. 2. Structure−Activity Relationship Studies of Aromatic Ring-Substituted Methylphenidate Analogs | volume=39 | issue=6 | pages=1201–1209 | date=15 March 1996 | url=https://pubs.acs.org/doi/10.1021/jm950697c | issn=0022-2623 | doi=10.1021/jm950697c}}</ref><ref>{{cite journal | vauthors=((Schweri, M. M.)), ((Deutsch, H. M.)), ((Massey, A. T.)), ((Holtzman, S. G.)) | journal=The Journal of Pharmacology and Experimental Therapeutics | title=Biochemical and behavioral characterization of novel methylphenidate analogs | volume=301 | issue=2 | pages=527–535 | date= May 2002 | issn=0022-3565 | doi=10.1124/jpet.301.2.527}}</ref><ref>{{cite journal | vauthors=((Davies, H. M. L.)), ((Hopper, D. W.)), ((Hansen, T.)), ((Liu, Q.)), ((Childers, S. R.)) | journal=Bioorganic & Medicinal Chemistry Letters | title=Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites | volume=14 | issue=7 | pages=1799–1802 | date=5 April 2004 | issn=0960-894X | doi=10.1016/j.bmcl.2003.12.097}}</ref><ref>{{cite journal | vauthors=((Misra, M.)), ((Shi, Q.)), ((Ye, X.)), ((Gruszecka-Kowalik, E.)), ((Bu, W.)), ((Liu, Z.)), ((Schweri, M. M.)), ((Deutsch, H. M.)), ((Venanzi, C. A.)) | journal=Bioorganic & Medicinal Chemistry | title=Quantitative structure-activity relationship studies of threo-methylphenidate analogs | volume=18 | issue=20 | pages=7221–7238 | date=15 October 2010 | issn=1464-3391 | doi=10.1016/j.bmc.2010.08.034}}</ref><ref>{{cite journal | vauthors=((Singh, S.)) | journal=Chemical Reviews | title=Chemistry, Design, and Structure−Activity Relationship of Cocaine Antagonists | volume=100 | issue=3 | pages=925–1024 | date=1 March 2000 | url=https://pubs.acs.org/doi/10.1021/cr9700538 | issn=0009-2665 | doi=10.1021/cr9700538}}</ref>

4F-MPH has an extremely short history of [[recreational drug use|recreational use]] and has yet to be documented being sold on the streets. It was initially developed as a replacement for [[ethylphenidate]] which became illegal in the United Kingdom on April 2015 following a temporary blanket ban. Shortly after, it became available for sale on the online gray market as a [[research chemical]] for global distribution.

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4F-MPH is thought to act primarily as a [[dopamine and norepinephrine]] [[reuptake inhibitor]], meaning it effectively boosts the levels of dopamine and norepinephrine [[neurotransmitters]] in the brain by binding to and partially blocking the transporter proteins that normally clear these catecholamines from the synaptic cleft. This allows dopamine and norepinephrine to accumulate within the reward pathways in the brain, resulting in stimulating and euphoric effects.

According to a pharmacological evaluation, the ''(±)-threo'' isomer of 4F-MPH is 2.15 times more effective at dopamine reuptake inhibition, and 2.7 times more at norepinephrine reuptake inhibition, than its parent compound methylphenidate. The ''(±)-erythro'' isomer, however, is 65 times less effective at dopamine reuptake inhibition and 45.6 times less effective at norepinephrine reuptake inhibition than methylphenidate. Neither racemate of 4F-MPH has a significant impact on serotonin reuptake.<ref>Analytical characterization and pharmacological evaluation of the new psychoactive substance 4-fluoromethylphenidate (4F-MPH) and differentiation between the (±)-threo and (±)-erythro diastereomers | https://~~analyticalsciencejournals.~~onlinelibrary.wiley.com/doi/~~abs~~/10.1002/dta.2167</ref>

According to a pharmacological evaluation, the ''(±)-threo'' isomer of 4F-MPH is 2.15 times more effective at dopamine reuptake inhibition, and 2.7 times more at norepinephrine reuptake inhibition, than its parent compound methylphenidate. The ''(±)-erythro'' isomer, however, is 65 times less effective at dopamine reuptake inhibition and 45.6 times less effective at norepinephrine reuptake inhibition than methylphenidate. Neither racemate of 4F-MPH has a significant impact on serotonin reuptake.<ref>{{cite journal | vauthors=((McLaughlin, G.)), ((Morris, N.)), ((Kavanagh, P. V.)), ((Power, J. D.)), ((Dowling, G.)), ((Twamley, B.)), ((O’Brien, J.)), ((Hessman, G.)), ((Murphy, B.)), ((Walther, D.)), ((Partilla, J. S.)), ((Baumann, M. H.)), ((Brandt, S. D.)) | journal=Drug Testing and Analysis | title=Analytical characterization and pharmacological evaluation of the new psychoactive substance 4-fluoromethylphenidate (4F-MPH) and differentiation between the (±)- threo and (±)- erythro diastereomers: Analytical characterization and pharmacological evaluation of 4-fluoromethylphenidate | volume=9 | issue=3 | pages=347–357 | date= March 2017 | url=https://onlinelibrary.wiley.com/doi/10.1002/dta.2167 | issn=19427603 | doi=10.1002/dta.2167}}</ref>

==Subjective effects==

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*'''Switzerland''': 4F-MPH is a controlled substance specifically named under Verzeichnis E.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>

*'''Turkey:''' 4F-MPH is a classed as drug and is illegal to possess, produce, supply, or import.<ref>Cumhurbaşkanı Kararı Karar Sayısı : 1335 | https://resmigazete.gov.tr/eskiler/2019/07/20190720-19.pdf</ref>

*'''United Kingdom''': 4-Fluoromethylphenidate is a class B drug in the UK as of 31st May 2017 and is illegal to possess, produce or supply. <ref>The Misuse of Drugs Act 1971 (Amendment) Order 2017 ~~(Legislation.gov.uk)~~ | ~~http~~://www.legislation.gov.uk/uksi/2017/634/made</ref>

*'''United Kingdom''': 4-Fluoromethylphenidate is a class B drug in the UK as of 31st May 2017 and is illegal to possess, produce or supply. <ref>{{Citation | title=The Misuse of Drugs Act 1971 (Amendment) Order 2017 | url=https://www.legislation.gov.uk/uksi/2017/634/made}}</ref>

*'''United States''': 4-Fluromethylphenidate is a Schedule I controlled substance in the state of Alabama.<ref>~~Controlled substances~~, ~~Schedule I, additional synthetic controlled substances and analogue substances included in, trafficking in controlled substance analogues, requisite weight increased, Secs. 13A-12-231~~, ~~20-2-23 am'd.~~ | https://legiscan.com/AL/text/SB333/~~2014~~</ref>

*'''United States''': 4-Fluromethylphenidate is a Schedule I controlled substance in the state of Alabama.<ref>{{Citation | title=Alabama SB333, 2014, Regular Session | url=https://legiscan.com/AL/text/SB333/id/988417}}</ref>

==See also==

@@ Line 4: / Line 4: @@
 '''4-Fluoromethylphenidate''' (commonly known as '''4F-MPH''') is a novel synthetic [[psychoactive class::stimulant]] of the [[chemical class::phenidate]] class that produces long-lasting [[Euphoria|euphoriant]], and [[stimulant|stimulating]] effects when [[Routes of administration|administered]]. It is a closely related structural analog of the commonly prescribed ADHD drug [[methylphenidate]] (known by the brand-names ''Ritalin'' and ''Concerta'').
-The two substances are believed to have very similar pharmacological mechanisms as [[monoamine]] [[reuptake inhibitors]] but have been reported to display distinctive [[subjective effects index|subjective effects]], with 4F-MPH being considered significantly more euphoric and recreational. Anecdotal reports suggest that it is considerably more potent with fewer uncomfortable side effects such as [[anxiety]], [[muscle spasms]] and [[compulsive redosing]].<ref>http://www.bluelight.org/vb/threads/770658-4-Fluoromethylphenidate-(4F-MPH)</ref> This perhaps owes to the fact that it has been shown to act as a higher efficiency [[dopamine]] reuptake inhibitor than the parent compound methylphenidate.<ref>Deutsch, H. M., Shi, Q., Gruszecka-Kowalik, E., & Schweri, M. M. (1996). Synthesis and pharmacology of potential cocaine antagonists. 2. Structure-activity relationship studies of aromatic ring-substituted methylphenidate analogs. Journal of medicinal chemistry, 39(6), 1201-1209. https://www.doi.org/10.1021/jm950697c</ref><ref>Biochemical and behavioral characterization of novel methylphenidate analogs (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/11961053</ref><ref>Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/15026075</ref><ref>Quantitative structure-activity relationship studies of threo-methylphenidate analogs (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/20846865</ref><ref>Chemistry, Design, and Structure−Activity Relationship of Cocaine Antagonists | http://pubs.acs.org/doi/abs/10.1021/cr9700538</ref>
+The two substances are believed to have very similar pharmacological mechanisms as [[monoamine]] [[reuptake inhibitors]] but have been reported to display distinctive [[subjective effects index|subjective effects]], with 4F-MPH being considered significantly more euphoric and recreational. Anecdotal reports suggest that it is considerably more potent with fewer uncomfortable side effects such as [[anxiety]], [[muscle spasms]] and [[compulsive redosing]].<ref>http://www.bluelight.org/vb/threads/770658-4-Fluoromethylphenidate-(4F-MPH)</ref> This perhaps owes to the fact that it has been shown to act as a higher efficiency [[dopamine]] reuptake inhibitor than the parent compound methylphenidate.<ref>{{cite journal | vauthors=((Deutsch, H. M.)), ((Shi, Q.)), ((Gruszecka-Kowalik, E.)), ((Schweri, M. M.)) | journal=Journal of Medicinal Chemistry | title=Synthesis and Pharmacology of Potential Cocaine Antagonists. 2. Structure−Activity Relationship Studies of Aromatic Ring-Substituted Methylphenidate Analogs | volume=39 | issue=6 | pages=1201–1209 | date=15 March 1996 | url=https://pubs.acs.org/doi/10.1021/jm950697c | issn=0022-2623 | doi=10.1021/jm950697c}}</ref><ref>{{cite journal | vauthors=((Schweri, M. M.)), ((Deutsch, H. M.)), ((Massey, A. T.)), ((Holtzman, S. G.)) | journal=The Journal of Pharmacology and Experimental Therapeutics | title=Biochemical and behavioral characterization of novel methylphenidate analogs | volume=301 | issue=2 | pages=527–535 | date= May 2002 | issn=0022-3565 | doi=10.1124/jpet.301.2.527}}</ref><ref>{{cite journal | vauthors=((Davies, H. M. L.)), ((Hopper, D. W.)), ((Hansen, T.)), ((Liu, Q.)), ((Childers, S. R.)) | journal=Bioorganic & Medicinal Chemistry Letters | title=Synthesis of methylphenidate analogues and their binding affinities at dopamine and serotonin transport sites | volume=14 | issue=7 | pages=1799–1802 | date=5 April 2004 | issn=0960-894X | doi=10.1016/j.bmcl.2003.12.097}}</ref><ref>{{cite journal | vauthors=((Misra, M.)), ((Shi, Q.)), ((Ye, X.)), ((Gruszecka-Kowalik, E.)), ((Bu, W.)), ((Liu, Z.)), ((Schweri, M. M.)), ((Deutsch, H. M.)), ((Venanzi, C. A.)) | journal=Bioorganic & Medicinal Chemistry | title=Quantitative structure-activity relationship studies of threo-methylphenidate analogs | volume=18 | issue=20 | pages=7221–7238 | date=15 October 2010 | issn=1464-3391 | doi=10.1016/j.bmc.2010.08.034}}</ref><ref>{{cite journal | vauthors=((Singh, S.)) | journal=Chemical Reviews | title=Chemistry, Design, and Structure−Activity Relationship of Cocaine Antagonists | volume=100 | issue=3 | pages=925–1024 | date=1 March 2000 | url=https://pubs.acs.org/doi/10.1021/cr9700538 | issn=0009-2665 | doi=10.1021/cr9700538}}</ref>
 F-MPH has an extremely short history of [[recreational drug use|recreational use]] and has yet to be documented being sold on the streets. It was initially developed as a replacement for [[ethylphenidate]] which became illegal in the United Kingdom on April 2015 following a temporary blanket ban. Shortly after, it became available for sale on the online gray market as a [[research chemical]] for global distribution.
@@ Line 20: / Line 20: @@
 F-MPH is thought to act primarily as a [[dopamine and norepinephrine]] [[reuptake inhibitor]], meaning it effectively boosts the levels of dopamine and norepinephrine [[neurotransmitters]] in the brain by binding to and partially blocking the transporter proteins that normally clear these catecholamines from the synaptic cleft. This allows dopamine and norepinephrine to accumulate within the reward pathways in the brain, resulting in stimulating and euphoric effects.
-According to a pharmacological evaluation, the ''(±)-threo'' isomer of 4F-MPH is 2.15 times more effective at dopamine reuptake inhibition, and 2.7 times more at norepinephrine reuptake inhibition, than its parent compound methylphenidate. The ''(±)-erythro'' isomer, however, is 65 times less effective at dopamine reuptake inhibition and 45.6 times less effective at norepinephrine reuptake inhibition than methylphenidate. Neither racemate of 4F-MPH has a significant impact on serotonin reuptake.<ref>Analytical characterization and pharmacological evaluation of the new psychoactive substance 4-fluoromethylphenidate (4F-MPH) and differentiation between the (±)-threo and (±)-erythro diastereomers | https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/dta.2167</ref>
+According to a pharmacological evaluation, the ''(±)-threo'' isomer of 4F-MPH is 2.15 times more effective at dopamine reuptake inhibition, and 2.7 times more at norepinephrine reuptake inhibition, than its parent compound methylphenidate. The ''(±)-erythro'' isomer, however, is 65 times less effective at dopamine reuptake inhibition and 45.6 times less effective at norepinephrine reuptake inhibition than methylphenidate. Neither racemate of 4F-MPH has a significant impact on serotonin reuptake.<ref>{{cite journal | vauthors=((McLaughlin, G.)), ((Morris, N.)), ((Kavanagh, P. V.)), ((Power, J. D.)), ((Dowling, G.)), ((Twamley, B.)), ((O’Brien, J.)), ((Hessman, G.)), ((Murphy, B.)), ((Walther, D.)), ((Partilla, J. S.)), ((Baumann, M. H.)), ((Brandt, S. D.)) | journal=Drug Testing and Analysis | title=Analytical characterization and pharmacological evaluation of the new psychoactive substance 4-fluoromethylphenidate (4F-MPH) and differentiation between the (±)- threo and (±)- erythro diastereomers: Analytical characterization and pharmacological evaluation of 4-fluoromethylphenidate | volume=9 | issue=3 | pages=347–357 | date= March 2017 | url=https://onlinelibrary.wiley.com/doi/10.1002/dta.2167 | issn=19427603 | doi=10.1002/dta.2167}}</ref>
 ==Subjective effects==
@@ Line 107: / Line 107: @@
 *'''Switzerland''': 4F-MPH is a controlled substance specifically named under Verzeichnis E.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
 *'''Turkey:''' 4F-MPH is a classed as drug and is illegal to possess, produce, supply, or import.<ref>Cumhurbaşkanı Kararı Karar Sayısı : 1335 | https://resmigazete.gov.tr/eskiler/2019/07/20190720-19.pdf</ref>
-*'''United Kingdom''': 4-Fluoromethylphenidate is a class B drug in the UK as of 31st May 2017 and is illegal to possess, produce or supply. <ref>The Misuse of Drugs Act 1971 (Amendment) Order 2017 (Legislation.gov.uk) | http://www.legislation.gov.uk/uksi/2017/634/made</ref>
+*'''United Kingdom''': 4-Fluoromethylphenidate is a class B drug in the UK as of 31st May 2017 and is illegal to possess, produce or supply. <ref>{{Citation | title=The Misuse of Drugs Act 1971 (Amendment) Order 2017 | url=https://www.legislation.gov.uk/uksi/2017/634/made}}</ref>
-*'''United States''': 4-Fluromethylphenidate is a Schedule I controlled substance in the state of Alabama.<ref>Controlled substances, Schedule I, additional synthetic controlled substances and analogue substances included in, trafficking in controlled substance analogues, requisite weight increased, Secs. 13A-12-231, 20-2-23 am'd. | https://legiscan.com/AL/text/SB333/2014</ref>
+*'''United States''': 4-Fluromethylphenidate is a Schedule I controlled substance in the state of Alabama.<ref>{{Citation | title=Alabama SB333, 2014, Regular Session | url=https://legiscan.com/AL/text/SB333/id/988417}}</ref>
 ==See also==