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When taken orally, L\u2010DOPS is converted to the sympathetic neurotransmitter, norepinephrine (NE), via decarboxylation catalyzed by L\u2010aromatic\u2010amino\u2010acid decarboxylase (LAAAD). Plasma L\u2010DOPS levels peak at about 3 h, followed by a monoexponential decline with a half\u2010time of 2 to 3 h. Plasma levels of NE and of its main neuronal metabolite, dihydroxyphenylglycol (DHPG) peak approximately concurrently but at much lower concentrations. The relatively long half\u2010time for disappearance of L\u2010DOPS from plasma, compared to that of NE, explains their very different attained plasma concentrations. In patients with neurogenic orthostatic hypotension, L\u2010DOPS increases blood pressure and ameliorates orthostatic intolerance. Inhibition of LAAAD, such as by treatment with carbidopa, which does not penetrate the blood\u2010brain barrier, prevents the blood pressure effects of the drug, indicating that L\u2010DOPS increases blood pressure by augmenting NE production outside the brain. Patients with pure autonomic failure (which usually entails loss of sympathetic noradrenergic nerves), and patients with multiple system atrophy (in which noradrenergic innervation remains intact) have similar plasma NE responses to L\u2010DOPS. This suggests mainly non\u2010neuronal production of NE from L\u2010DOPS. L\u2010DOPS is very effective in treatment of deficiency of dopamine\u2010beta\u2010hydroxylase (DBH), the enzyme required for conversion of dopamine to NE in sympathetic nerves. L\u2010DOPS holds promise for treating other much more common conditions involving decreased DBH activity or NE deficiency, such as a variety of syndromes associated with neurogenic orthostatic hypotension.<\/jats:p>","DOI":"10.1111\/j.1527-3466.2006.00189.x","type":"journal-article","created":{"date-parts":[[2007,1,2]],"date-time":"2007-01-02T17:57:03Z","timestamp":1167760623000},"page":"189-203","source":"Crossref","is-referenced-by-count":84,"title":["L\u2010Dihydroxyphenylserine (L\u2010DOPS): A Norepinephrine Prodrug"],"prefix":"10.1111","volume":"24","author":[{"given":"David 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