Catecholamine metabolism during additional administration of DL-threo-3,4-dihydroxyphenylserine to patients with Parkinson's disease.
DL-threo-3,4-dihydroxyphenylserine (DL-threo-DOPS) was administered during 10 days to 4 patients with longstanding Parkinson's disease in addition to their treatment with L-3,4-dihydroxyphenyl-L-alanine (L-DOPA)-carbidopa (Sinemet). All patients tended to improve in their symptoms freezing, all day life activity and mood. There were no improvements in rigidity, tremor, and akinesia (in general). During the DL-threo-DOPS-treatment cerebrospinal fluid (CSF), serum and urine concentrations of catecholamines were measured. The results show that DL-threo-DOPS is transported to the brain and CSF in a way comparable with L-DOPA. However, no measurable increase of 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG) in CSF could be demonstrated. This suggests that the synthesis of noradrenaline from DL-threo-DOPS in the brain is doubtful. In addition measurements in urine reveals that at the dose used Sinemet prevents peripheral decarboxylation of DL-threo-DOPS into noradrenaline. Other possible metabolic pathways of DL-threo-DOPS are discussed.
Teelken
A W
AW
Department of Neurology, University Hospital, Groningen, The Netherlands.
van den Berg
G A
GA
Muskiet
F A
FA
Staal-Schreinemachers
A L
AL
Wolthers
B G
BG
Lakke
J P
JP
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000368:Aged; D002395:Catecholamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D015103:Droxidopa / Q000627:therapeutic use*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000378:metabolism; D012694:Serine / Q000031:analogs & derivatives*
D002395:Catecholamines; D015102:3,4-Dihydroxyphenylacetic Acid; D012694:Serine; D006897:Hydroxyindoleacetic Acid; D015103:Droxidopa; D004298:Dopamine; D006719:Homovanillic Acid