Tetrahydrobiopterin administration to rhesus macaques. Its appearance in CSF and effect on neurotransmitter synthesis

Tetrahydrobiopterin, the hydroxylase cofactor (BH4) was administered (i.v. 20 mg/kg) to Rhesus monkeys. Within 90 min of its administration CSF cofactor levels increased significantly above baseline levels. Peak CSF levels were attained at 90-180 min time period following cofactor injection and returned to baseline gradually over the next 15 hrs. The increased brain cofactor levels had no apparent effect on synthesis of dopamine, norepinephrine or serotonin as evidenced by a lack of change in the levels of the metabolites homovalillic acid, 3-methoxy-4-hydroxyphenyleneglycol, and 5-hydroxyindoleacetic acid. The present results using primates suggest no apparent effect of increased cofactor levels on monoamine biosynthesis. However, it remains to be explored whether monoamine synthesis could be affected by increased cofactor levels in the pathological situation.