Pyridoxine, dopa decarboxylase, and tetrahydroisoquinoline derivatives in Parkinson’s disease

Summary

The activity of pyridoxal phosphate-dependent dopa decarboxylase in the corpus striatum of patients with Parkinson’s disease is low. However, pyridoxine which nullifies the beneficial therapeutic effects oflevodopa is contraindicated in patients with Parkinson’s disease. This problem is obviated by carbidopa, a peripheral dopa decarboxylase inhibitor which does not penetrate the blood brain barrier and hence does not affect the formation of dopamine in the brain. Administration of pyridoxine enhances the synthesis of cysteine and dopamine in the brain, and oxidation of dopamine in the presence of cysteine generates neurotoxic products such as dihydrobenzothiazines. Moreover, the situation is aggravated by the fact that the concentration of glutathione, a cysteine containing peptide, is low in the striatum of Parkinsonian patients. In addition, pyridoxal-containing tetrahydroisoquinoline derivatives, alter mitochondrial functions by inhibiting the activity of complex I. Therefore, pyridoxine should be used cautiously in patients with Parkinson’s disease.