Reversal of .ALPHA.-Methyltyrosine-Induced Hypoactivity by 6-(R)-5,6,7,8-Tetrahydro-L-Erythrobiopterin (R-THBP) in Mice.

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The effects of peripheral administration of 6-(<I>R</I>)-5, 6, 7, 8-tetrahydro-L-erythrobiopterin dihydrochloride (R-THBP), a natural cofactor for tyrosine and tryptophan hydroxylases, were investigated in mice treated with a competitive inhibitor of tyrosine hydroxylase, α-methyltyrosine (α-MT). A subcutaneous dose of 250 mg/kg of α-MT decreased markedly both ambulatory activity and cerebral contents of norepinephrine, dopamine and their metabolites in mice. An intraperitoneal dose of 100 mg/kg of R-THBP, which did not alter ambulatory activities in normal mice, improved the hypoactivity in α-MT-treated mice. Moreover, R-THBP at intraperitoneal doses of 60 and 100 mg/kg inhibited the impairment of cerebral catecholamine metabolism induced by α-MT in mice. We suggest that the reversal of the α-MT effects by R-THBP might be due to reactivation of tyrosine hydroxylase in the central nervous system.
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