Methylphenidate (MPH) is a dopamine and norepinephrine reuptake inhibitor. It is the racemic mixture of d-MPH and l-MPH. According to the binding profile info on Wikipedia, based on studies, it is at least 6 times more potent at inhibiting the dopamine transporter (DAT) than the norepinephrine transporter (NET).

The dextrorotatory enantiomer, d-MPH, is said to be the main responsible for the therapeutic response of methylphenidate, and to be "much more bioavailable than levomethylphenidate when administered orally" (this paper from 1999 is given as reference). I read it "can be anticipated to be twice the strenght of the racemic product". One distinct property of d-MPH is that it is much less selective for DAT inhibition as opposed to dl-MPH - in fact, it is a bit more potent at inhibiting the NET (at a ratio of about 1.2 - 1.3) compared to the DAT).
The way I see it, this may have clinical significance since dopamine reuptake in the prefrontal cortex is mainly carried by the NET, since DAT expression is significantly lower in this region of the brain [1] [2].

The Wikipedia article also states that "Coingestion of alcohol (ethanol) also increases the blood plasma levels of d-methylphenidate by up to 40%". It references this study from 2011.

What I want to know is: Does that all mean that the ingestion of alcohol, when taking (racemic) methylphenidate can actually make it more potent, at least at lower doses?
Of course, alcohol has an increased activity effect on GABA receptors, which complicates things.



1 Answer 1


Does the ingestion of alcohol, when taking (racemic) methylphenidate can actually make it more potent?

It is the 2011 study you've mentioned that answers most of the question.

In the study, ethanol co-ingestion with racemic MPH elevated maximal plasma levels of d-MPH by up to 40%. The participants reported greater stimulant effect after alcohol + MPH than after MPH alone (Table 2).

Now, the completely different question is if such combination of alco + MPH is also beneficial and safe.


MPH–ethanol coabuse has been widely reported in both annual Drug Abuse Warning Network data and the clinical literature.


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