The effects of L-threo-dihydroxyphenylserine on norepinephrine metabolism in rat brain.
The effects of L-threo-3,4-dihydroxyphenylserine (DOPS), an artificial precursor of norepinephrine (NE), on NE metabolism in rat brain were investigated. DOPS administration resulted in a significant elevation in cerebral NE and 3-methoxy-4-hydroxyphenylglycol contents, while carbidopa pretreatment completely blocked these increases. After brain NE was depleted by either alpha-methyl-p-tyrosine (AMPT), fusaric acid, FLA-63, or reserpine, NE restoration by DOPS was observed in rats treated with either fusaric acid or chronic reserpine. No NE restoration was observed after pretreatment with AMPT, FLA-63, or acute reserpine. The results suggest that NE formed after DOPS administration is mainly localized in the brain capillaries. In some NE-depleting conditions, however, DOPS can penetrate the brain parenchyma.
D000818:Animals; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D002230:Carbidopa / Q000494:pharmacology; D015103:Droxidopa / Q000494:pharmacology*; D005669:Fusaric Acid / Q000494:pharmacology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D008781:Methyltyrosines / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D012694:Serine / Q000031:analogs & derivatives*; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D012694:Serine; D008734:Methoxyhydroxyphenylglycol; D019805:alpha-Methyltyrosine; D012110:Reserpine; D015103:Droxidopa; D005669:Fusaric Acid; D002230:Carbidopa; D009638:Norepinephrine