A Comprehensive Monograph on Metadoxine (DB16554)

1.0 Executive Summary

Metadoxine is a small molecule drug with a unique chemical identity as an ion-pair salt of pyridoxine (vitamin B6) and L-2-pyrrolidone-5-carboxylate (pyroglutamic acid). This composition underpins a multifaceted mechanism of action that confers both hepatoprotective and neuromodulatory effects. The drug's primary therapeutic application, established over decades of use in several European and other nations, is in the management of acute and chronic alcohol-related disorders. Clinical evidence supports its efficacy in accelerating the clearance of ethanol and its toxic metabolite, acetaldehyde, thereby shortening recovery time from acute intoxication. Furthermore, it has demonstrated significant utility in treating alcoholic liver disease, including alcoholic fatty liver and severe alcoholic hepatitis, where it improves liver function, reduces steatosis, and has been shown to improve short-term survival when used as an adjunct to standard therapy. A notable feature is its apparent efficacy even in patients who have not achieved complete abstinence from alcohol.

The pharmacological profile of Metadoxine is complex. Its hepatoprotective actions are attributed to the restoration of hepatic glutathione and adenosine triphosphate (ATP) levels, antioxidant effects that mitigate oxidative stress, and anti-inflammatory properties such as the attenuation of TNF-α secretion. Concurrently, its neuromodulatory effects are linked to its activity as a modulator of the GABAergic system—by inhibiting GABA transaminase and enhancing GABAergic transmission—and as a selective antagonist of the 5-HT2B serotonin receptor.