Biochemical and behavioural indices of striatal dopaminergic activity after 6-methyltetrahydropterin

The biochemical effects of 6-methyltetrahydropterin (6-MPH4), a synthetic analogue of tetrahydrobiopterin (BH4), the hydroxylase cofactor, were investigated on striatal dopaminergic neurons in the rat. Although a single parenteral dose of 6-MPH4 (18 or 54 mg/kg) did not significantly increase the content of dopamine (DA) or its acidic metabolites, L-didrohyphenylanine (L-DOPA) accumulation after decarboxylase inhibition was evident in rats receiving 54 mg/kg of 6-MPH4. On the other hand, 6-MPH4 (18 mg/kg) potentiated the reserpine-induced DA metabolism as demonstrated by increased HVA levels. In a behavioural test, 6-MPH4 partially prevented haloperidol-induced catalepsy. BH4 concentrations could thus be subsaturating with respect to tyrosine hydroxylase (TH), particularly when the enzyme activity is stimulated and the results suggest that cofactor supply may have pharmacological significance.