3,4-Dichloromethylphenidate
- none
- CA: Schedule III
- DE: NpSG (Industrial and scientific use only)
- UK: Class B
- Methyl 2-(3,4-dichlorophenyl)-2-(piperidin-2-yl)acetate
- 1400742-68-8
Y
- 44418862
- 23278471
Y
- F7LN3N6ZLA
- DTXSID30658831
- Interactive image
- COC(=O)C(c1ccc(c(c1)Cl)Cl)C2CCCCN2
- 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
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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. It has been sold online as a designer drug.[1][2]
Chemistry
3,4-DCMP is an analogue of methylphenidate which was chlorinated at the meta- and para- positions on the phenyl ring. This results in dramatically increased potency, duration, and a huge increase in affinity for the serotonin transporter and serotonin uptake inhibition. Serotoninergic 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 (in the case of the aforementioned compounds, a 2-naphthalene ring) which mimicks the bicyclic indole ring system of serotonin.
Pharmacology
Pharmacokinetics
3,4-DCMP most likely follows a similar metabolic fate as methylphenidate, primarily through hydrolysis of the ester bond into 3,4-dichloro-ritalinic acid, which is then primarly excreted in urine.
Pharmacodynamics
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]
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
References
- ^ Wood S (10 April 2015). "Temporary Class Drug Order – legal highs' bubble to be 'burst'". Criminal Law Blog: Kingsley Napley.
- ^ a b c Froimowitz M, Gu Y, Dakin LA, Nagafuji PM, Kelley CJ, Parrish D, et al. (January 2007). "Slow-onset, long-duration, alkyl analogues of methylphenidate with enhanced selectivity for the dopamine transporter". Journal of Medicinal Chemistry. 50 (2): 219–232. doi:10.1021/jm0608614. PMID 17228864.
- ^ Wayment HK, Deutsch H, Schweri MM, Schenk JO (March 1999). "Effects of methylphenidate analogues on phenethylamine substrates for the striatal dopamine transporter: potential as amphetamine antagonists?". Journal of Neurochemistry. 72 (3): 1266–1274. doi:10.1046/j.1471-4159.1999.0721266.x. PMID 10037500. S2CID 26220081.
- ^ Deutsch HM, Shi Q, Gruszecka-Kowalik E, Schweri MM (March 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. doi:10.1021/jm950697c. PMID 8632426.
- ^ a b Schweri MM, Deutsch HM, Massey AT, Holtzman SG (May 2002). "Biochemical and behavioral characterization of novel methylphenidate analogs". The Journal of Pharmacology and Experimental Therapeutics. 301 (2): 527–535. doi:10.1124/jpet.301.2.527. PMID 11961053.
- ^ Kim DI, Deutsch HM, Ye X, Schweri MM (May 2007). "Synthesis and pharmacology of site-specific cocaine abuse treatment agents: restricted rotation analogues of methylphenidate". Journal of Medicinal Chemistry. 50 (11): 2718–2731. doi:10.1021/jm061354p. PMID 17489581.
- ^ Wayment HK, Deutsch H, Schweri MM, Schenk JO (March 1999). "Effects of methylphenidate analogues on phenethylamine substrates for the striatal dopamine transporter: potential as amphetamine antagonists?". Journal of Neurochemistry. 72 (3): 1266–1274. doi:10.1046/j.1471-4159.1999.0721266.x. PMID 10037500.
- ^ "关于印发《非药用类麻醉药品和精神药品列管办法》的通知" (in Chinese). China Food and Drug Administration. 27 September 2015. Archived from the original on 1 October 2015. Retrieved 1 October 2015.
- ^ Methylphenidate-based NPS: A review of the evidence of use and harm. Advisory Council on the Misuse of Drugs, 31 March 2015
- ^ "Cannabinoider föreslås bli klassade som hälsofarlig vara". Retrieved 29 June 2015.
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