3,4-Dichloromethylphenidate

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.

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 serotonergic activity, the other two being HDMP-28 & HDEP-28. The reason for the serotonergic 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 serotonergic activity include naphthylaminopropane and 3,4-dichloroamphetamine.

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.

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. However, H. M. Deutsch's discrimination ratio 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.

Legality

As of November 2016 3,4-DCMP (aka 3,4-CTMP) is now included in Canada's CDSA as a schedule III substance.

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

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

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

References

References

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10. "Cannabinoider föreslås bli klassade som hälsofarlig vara".