Ethylphenidate is a psychostimulant and a close analog of methylphenidate. Ethylphenidate acts as both a dopamine reuptake inhibitor and norepinephrine reuptake inhibitor, meaning it effectively boosts the levels of the norepinephrine and dopamine neurotransmitters in the brain, by binding to, and partially blocking the transporter proteins that normally remove those monoamines from the synaptic cleft. However, considering the close similarities between ethylphenidate and methylphenidate and the fact that methylphenidate, like cocaine, actually does not primarily act as a "classical" reuptake inhibitor, but rather as an "inverse agonist at the DAT", it is at least very likely that ethylphenidate also primarily acts as an inverse DAT agonist instead of as a classical reuptake inhibitor. There have been anecdotal reports of a perforated septum resulting from even just a few uses of ethylphenidate by insufflation. Some users also report the drug is extremely painful to insufflate.
Pharmacokinetics
Ethylphenidate metabolizes into methylphenidate and ritalinic acid. Tiny amounts of ethylphenidate can be formed in vivo when alcohol and methylphenidate are coingested, via hepatictransesterification. Ethylphenidate formation appears to be more common when large quantities of methylphenidate and alcohol are consumed at the same time, such as in non-medical use or overdose scenarios. However, the transesterfication process of methylphenidate to ethylphenidate, as tested in mice liver, was dominant in the inactive -enantiomer but showed a prolonged and increased maximal plasma concentration of the active -enantiomer of methylphenidate. Additionally, only a few percent of the consumed methylphenidate is converted to ethylphenidate. This carboxylesterase-dependent transesterification process is also known to occur when cocaine and alcohol are consumed together, forming cocaethylene.
Pharmacodynamics
All available data on ethylphenidate's pharmacokinetics are drawn from studies conducted on rodents. Ethylphenidate is more selective to the dopamine transporter than methylphenidate, having approximately the same efficacy as the parent compound, but has significantly less activity on the norepinephrine transporter. Its dopaminergicpharmacodynamic profile is nearly identical to methylphenidate, and is primarily responsible for its euphoric and reinforcing effects. The eudysmic ratio for ethylphenidate is superior to that of methylphenidate. The following is ethylphenidate's binding profile in the mouse, alongside methylphenidate's. Figures for both the racemic and the dextrorotary enantiomers are given:
Ethylphenidate is not controlled in the Netherlands, as the Opium Law does not cover it, nor is there any law covering analogs of controlled drugs. At the 16th of March 2017 the decision was made to start including Ethylphenidate in the Opium Law in the near future.
Ethylphenidate is not explicitly controlled in US but it could possibly be considered an analog of a Schedule II substance under the Federal Analog Act if sold for human consumption.
Ethylphenidate is illegal in Sweden as of 15 December 2012.
Ethylphenidate is illegal to manufacture, distribute or import in the UK, as of 10 April 2015 it has been placed under a Temporary Class Drug Order which automatically places it in a Class-B-like category. Though ordinarily the TCDO would only last 1 year, the ACMD reported that since its invocation prevalence of MPA had significantly decreased, and that it had been challenging to collect information about the drug. As a result of this, they requested that the TCDO be extended a further year from 26 June 2016.
Ethylphenidate is illegal in Jersey under the Misuse of Drugs Law 1978.
Australian state and federal legislation contains provisions that mean that analogues of controlled drugs are also covered by the legislation. Ethylphenidate would be an analogue of methylphenidate under this legislation.
