Para-aminosalicylic acid in the treatment of manganese toxicity

Manganese excess associated with occupational and environmental exposure can induce acute effects, with a syndrome known as manganism, similar for a number of symptoms to Parkinson’s disease. A possible remedy should be chelation therapy. Paraaminosalicylic acid (PAS) in its use in China demonstrated effective in reducing symptoms of manganism. There is evidence of a Nacetylated metabolite (AcPAS) that seems effective in reducing manganese levels in brain. Based on these reports we studied the protonation and the complex formation equilibria of PAS and of AcPAS with the target metal ion Mn2+. This study has documented a substantial Mn chelating potential of both ligands. In the actual case, the metabolism of PAS leads to a derivative with unusual stronger chelating ability than the parent molecule. It is presumed that the relatively small molecule Ac-PAS can penetrate across the blood-to-brain border and exert its Mn2+ mobilizing action intracellularly.