[1] Pyridoxine (vitamin B6) is a precursor of coenzymes including pyridoxal 5’-phosphate (PLP), which accelerates the metabolic degradation of ethanol and prevents adenosine triphosphate (ATP) inactivation by acetaldehyde.

Pyridoxal phosphate dependent enzymes also play a role in the biosynthesis of four important neurotransmitters: serotonin (5-HT), epinephrine, norepinephrine and GABA: see vitamin B6 functions.

[4] Metadoxine may block the differentiation step of preadipocytes by inhibiting CREB phosphorylation and binding to the cAMP response element, thereby repressing CCAAT/enhancer-binding protein b during hormone-induced adipogenesis.

[8] Several Phase II ADHD studies demonstrated a consistent signal of efficacy reaching statistical significance, as measured by neuropsychological testing (such as the computerized Test of Variables of Attention (TOVA) in acute settings) and clinical scales (in chronic administration studies), with no treatment-related serious adverse events or major differences in adverse events profiles between drug and placebo groups.

The failure announcement came a week after Alcobra won FDA agreement to review data collected to date in the MEASURE study and consider it in a future NDA submission of MDX for ADHD.

The FDA also agreed to change a full clinical hold for the trial to a partial clinical hold pending review and approval of the company's proposed protocol for a 6-month, Phase I study to assess the potential relevance of adverse findings observed in long-term animal studies of metadoxine in relation to human exposure, Alcobra said.

Metadoxine also demonstrated restoration of abnormal neuronal morphology as well as reduced the exaggerated basal protein production, both implicated in the pathophysiology of FXS and presumed to be responsible for impaired learning and memory.