3,4-Dichloromethylphenidate

3,4-DCMP is the 3,4-dichlorinated analogue of methylphenidate. The 3,4-dichlorination is a common modification done to most monoamine reuptake inhibitors.{{Citation needed|date=June 2025}}

The result of the 3,4-dichlorination on 3,4-DCMP is a higher selectivity for the serotonin transporter and serotonin uptake inhibition. Serotonergic activity among phenidates is very rare, and 3,4-DCMP is one of only three compounds from this class with appreciable serotoninergic activity, the other two being HDMP-28 & HDEP-28. The reason for the serotoninergic activity of all three compounds is a bulky aryl ring system (in the case of the aforementioned compounds, a 2-naphthalene ring), which mimics the bicyclic indole ring system of serotonin. Examples of compounds with the same SAR modifictions done to increase serotoninergic activity include naphthylaminopropane and [[3,4-Dichloroamphetamine|3,4-dichloroamphetamine.{{Citation needed|date=June 2025}}

The 3,4-dichloro group also increases resistance to metabolism, which can be seen on the compound's greatly increased duration of action and biological half-life. Furthermore, it also results in a greatly increased affinity for both the dopamine and noradrenaline transporters, because the 3,4-dichloro group more closely mimics the 3,4-dihydroxy group found on dopamine and adrenaline. Examples of compounds with the same SAR modification done to increase affinity to DAT & NET include dichloropane and O-2390.{{Citation needed|date=June 2025}}

3,4-CTMP, the d,l-threo diastereomer of 3,4-DCMP, is approximately seven times more potent than methylphenidate in animal studies, but has weaker reinforcing effects due to its slower onset of action.{{cite journal | vauthors = Wayment HK, Deutsch H, Schweri MM, Schenk JO | title = Effects of methylphenidate analogues on phenethylamine substrates for the striatal dopamine transporter: potential as amphetamine antagonists? | journal = Journal of Neurochemistry | volume = 72 | issue = 3 | pages = 1266–1274 | date = March 1999 | pmid = 10037500 | doi = 10.1046/j.1471-4159.1999.0721266.x | s2cid = 26220081 | doi-access = free }}{{cite journal | vauthors = Deutsch HM, Shi Q, Gruszecka-Kowalik E, Schweri MM | title = Synthesis and pharmacology of potential cocaine antagonists. 2. Structure-activity relationship studies of aromatic ring-substituted methylphenidate analogs | journal = Journal of Medicinal Chemistry | volume = 39 | issue = 6 | pages = 1201–1209 | date = March 1996 | pmid = 8632426 | doi = 10.1021/jm950697c }}{{cite journal | vauthors = Schweri MM, Deutsch HM, Massey AT, Holtzman SG | title = Biochemical and behavioral characterization of novel methylphenidate analogs | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 301 | issue = 2 | pages = 527–535 | date = May 2002 | pmid = 11961053 | doi = 10.1124/jpet.301.2.527 }}{{cite journal | vauthors = Kim DI, Deutsch HM, Ye X, Schweri MM | title = Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 11 | pages = 2718–2731 | date = May 2007 | pmid = 17489581 | doi = 10.1021/jm061354p }}{{cite journal | vauthors = Wayment HK, Deutsch H, Schweri MM, Schenk JO | title = Effects of methylphenidate analogues on phenethylamine substrates for the striatal dopamine transporter: potential as amphetamine antagonists? | journal = Journal of Neurochemistry | volume = 72 | issue = 3 | pages = 1266–1274 | date = March 1999 | pmid = 10037500 | doi = 10.1046/j.1471-4159.1999.0721266.x }} However, H. M. Deutsch's discrimination ratio{{Clarification needed|date=June 2019}} implies it to be more reinforcing than cocaine.

• ¹ This is an abbreviation of the d,l-erythro diastereomer of 3,4-DCMP.
• ² This is an abbreviation of d,l-threomethylphenidate, more widely known by its brand name Ritalin.

As of October 2015 3,4-CTMP is a controlled substance in China.{{cite web | url=http://www.sfda.gov.cn/WS01/CL0056/130753.html | title=关于印发《非药用类麻醉药品和精神药品列管办法》的通知 | publisher=China Food and Drug Administration | date=27 September 2015 | language=zh | access-date=1 October 2015 | archive-url=https://web.archive.org/web/20151001222554/http://www.sfda.gov.cn/WS01/CL0056/130753.html | archive-date=1 October 2015 | url-status=dead }}

3,4-CTMP was banned in the UK as a Temporary Class Drug from April 2015 following its unapproved sale as a designer drug.[https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/420983/TCDO_methylphenidate_NPS.pdf Methylphenidate-based NPS: A review of the evidence of use and harm. Advisory Council on the Misuse of Drugs, 31 March 2015]

Sweden's public health agency suggested to classify 3,4-CTMP as hazardous substance on 10 November 2014.{{cite web | url=http://www.folkhalsomyndigheten.se/nyheter-och-press/nyhetsarkiv/2014/november/cannabinoider-foreslas-bli-klassade-som-halsofarlig-vara/ | title=Cannabinoider föreslås bli klassade som hälsofarlig vara | access-date=29 June 2015}}

• 3-Bromomethylphenidate
• 4-Methylmethylphenidate
• Cilobamine
• Dichloropane
• HDEP-28
• HDMP-28
• Isopropylphenidate
• LR-5182
• O-2390
• Propylphenidate

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{{Stimulants}}

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Category:Stimulants

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Category:2-Piperidinyl compounds

Category:Chloroarenes

Category:Methyl esters