Summary
In the 1950s it was found that an artificial aminoacid, 3,4-threo-dihydroxyphenylserine (DOPS), was converted to norepinephrine (NE) in a single step by the enzyme L-aromatic amino acid decarboxylase (AADC), bypassing the need for the rate limiting enzyme dopamine beta hydroxylase. Trying to replicate the success of dihydroxyphenylalanine (DOPA) in the treatment of Parkinson disease, treatment with DOPS was attempted in patients with autonomic failure who have impaired NE release. DOPS improved orthostatic hypotension in patients with familial amyloid polyneuropathy, congenital deficiency of dopamine beta hydroxylase, pure autonomic failure and multiple system atrophy. DOPS pressor effect is due to its conversion to NE outside the central nervous system because concomitant administration of carbidopa, an inhibitor of AADC that does not cross the blood-brain barrier, blunted both the increase in plasma NE and the pressor response. DOPS pressor response is not dependent on intact sympathetic terminals because its conversion to NE also occurs in non-neuronal tissues.
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Kaufmann, H. (2006). The discovery of the pressor effect of DOPS and its blunting by decarboxylase inhibitors. In: Riederer, P., Reichmann, H., Youdim, M.B.H., Gerlach, M. (eds) Parkinson’s Disease and Related Disorders. Journal of Neural Transmission. Supplementa, vol 70. Springer, Vienna . https://doi.org/10.1007/978-3-211-45295-0_71
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DOI: https://doi.org/10.1007/978-3-211-45295-0_71
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