Toxic optic neuropathy: Psychotropics and ethambutol inhibit myelin basic protein phosphorylation

It has been suggested that phosphorylation of myelin basic protein (MBP) modulates the structure and function of myelin. MBP is demonstrated to be phosphorylated by protein kinase C (PKC) and cyclic AMP-dependent protein kinase (PICA) in the central nervous system. The effects of lipid-soluble psychotropics and ethambutol on phosphorylation of MBP were examined. Chlorpromazine and imipramine inhibit PKC-catalyzed reaction but not PKA phosphorylation. Inhibition of activity levels (IC50) for these drugs were 0.1 and 0.5 mM, respectively. Ethambutol has an inhibitory effect on PKA-catalyzed phosphorylation of MBP but has no effect on PKC-catalyzed reactions. Ethambutol displayed a much higher IC50 of 6 mM. It is possible that inhibitory effects of drugs on phosphorylation of MBP may be involved in the pathogenesis of toxic optic neuropathy.