Ethylphenidate (EP) is a potent psychostimulant that 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.

It is most commonly formed when ethanol and methylphenidate are coingested, via hepatic transesterification. 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. This carboxylesterase-dependent transesterification process is also known to occur when cocaine and alcohol are consumed together, forming cocaethylene.

Ethylphenidate is more selective to the dopamine transporter (DAT) than methylphenidate, having approximately the same efficacy as the parent compound, but has significantly less activity on the norepinephrine transporter (NET). It has a near-identical dopaminergic pharmacodynamic profile as methylphenidate, which is primarily responsible for its euphoric and reinforcing effects.

The eudysmic ratio for ethylphenidate is superior to that of methylphenidate.

Compound Binding DAT Binding NET Uptake DA Uptake NE
d-TMP 139 408 28 46
d-TEP 276 2479 24 247
dl-TMP 105 1560 24 31
dl-TEP 382 4824 82 408

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