3,4-Dichloromethylphenidate

3,4-dichloromethylphenidate (abbreviated as 3,4-DCMP, and incorrectly as 3,4-CTMP for the d,l-threo diastereomer) is a potent stimulant drug from the phenidate class closely related to methylphenidate. It acts as a potent serotonin-norepinephrine-dopamine reuptake inhibitor with a long duration of action.^{[clarification needed]} It has been sold online as a designer drug.^[1][2]

3,4-DCMP

Clinical data
Routes of administration	oral, insufflation, rectal
ATC code	none
Legal status
Legal status	CA: Schedule III DE: NpSG (Industrial and scientific use only) UK: Class B
Pharmacokinetic data
Metabolism	Primarily by the liver
Excretion	Predominantly renal
Identifiers
IUPAC name Methyl 2-(3,4-dichlorophenyl)-2-(piperidin-2-yl)acetate
CAS Number	1400742-68-8 Y
PubChem CID	44418862
ChemSpider	23278471 Y
UNII	F7LN3N6ZLA
CompTox Dashboard (EPA)	DTXSID30658831
Chemical and physical data
Formula	C14H17Cl2NO2
Molar mass	302.20 g·mol−1
3D model (JSmol)	Interactive image
SMILES COC(=O)C(c1ccc(c(c1)Cl)Cl)C2CCCCN2
InChI InChI=1S/C14H17Cl2NO2/c1-19-14(18)13(12-4-2-3-7-17-12)9-5-6-10(15)11(16)8-9/h5-6,8,12-13,17H,2-4,7H2,1H3 Y Key:JUKMAYKVHWKRKY-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Chemistry

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]}

Pharmacology

Pharmacodynamics

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 modifications done to increase serotoninergic activity include naphthylaminopropane and 3,4-dichloroamphetamine.^{[citation needed]}

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]}

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.^{[2][3][4][5][6][7]} However, H. M. Deutsch's discrimination ratio^{[clarification needed]} implies it to be more reinforcing than cocaine.^[5]

Inhibition of [¹²⁵I]RTI-55 Binding and [³H]Monoamine Uptake of 3,4-DCMP diastereomers, and related compounds.^[2]

Compound	DAT (Ki, nM)	DA uptake IC50 (nM)	SERT (Ki, nM)	5HT uptake IC50 (nM)	NET (Ki, nM)	NE uptake IC50 (nM)	NET/DAT selectivity	NE/DA uptake selectivity
3,4-CTMP	1.4 ± 0.1	23 ± 3	1,600 ± 150	540 ± 110	14 ± 6	10 ± 1	10.0	0.43
3,4-CEMP1	90 ± 14	800 ± 110	2,500 ± 420	1,100 ± 90	4,200 ± 1,900	190 ± 50	46.7	0.24
TMP2	110 ± 9	110 ± 9	65,000 ± 4,000	5,100 ± 7,000	660 ± 50	61 ± 14	6.0	0.77
Cocaine	500 ± 65	240 ± 15	340 ± 40	250 ± 40	500 ± 90	210 ± 30	1.0	0.88

• 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.

Legality

As of October 2015 3,4-CTMP is a controlled substance in China.^[8]

3,4-CTMP was banned in the UK as a Temporary Class Drug from April 2015 following its unapproved sale as a designer drug.^[9]

Sweden's public health agency suggested to classify 3,4-CTMP as hazardous substance on 10 November 2014.^[10]

See also

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