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Human brain dopamine metabolism in levodopa-induced dyskinesia and wearing-off.
Parkinsonism Relat Disord. 2004 Jun; 10(4):221-6.PR

Abstract

The objective of this study was to identify dopamine (DA) metabolism pattern in Lewy body Parkinson's disease (PD) patients with dyskinesia (Dysk) only, with wearing-off (WO) only, or no motor complications (NMC) induced by levodopa (LD). DA, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3-methoxytyramine (3-MT) were measured individual basal ganglia nuclei of nine PD patients who received LD for 6-18 years. Three patients had only Dysk, three only WO, and three had neither Dysk nor WO. Biochemical measurements in PD brains were compared with four non-neurological control brains from individuals matched for age and post-mortem retrieval time. DA levels in the PD were reduced in the caudate by 87% and putamen by 99%. In the caudates, the HVA/DA molar ratio as an index of DA metabolism was similar in the WO and the Dysk patients. However, in the putamen, the ratio of HVA/DA was significantly higher in the WO compared with the Dysk (p = 0.03)and the NMC (p = 0.04) groups of patients. In the putamen, the DOPAC levels were higher in the WO cases while in the Dysk cases, 3-MT levels were higher. The results suggest that in the WO only cases, the putaminal DA was in large measure metabolized intraneuronally while the DA metabolism in our Dysk only patients was mainly extraneuronal. We conclude that the magnitude and the site (intra vs. extraneuronal) of the synaptic DA metabolism in the putamen plays a significant role in LD-induced Dysk and WO.

Authors+Show Affiliations

Division of Neurology, University of Saskatchewan and Saskatoon Health Region, Rm 1663, Royal University Hospital, 103 Hospital Drive, Saskatoon, Saskatchewan, Canada S7N 0W8. ali.rajput@saskatoonhealthregion.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15120096

Citation

Rajput, Ali H., et al. "Human Brain Dopamine Metabolism in Levodopa-induced Dyskinesia and Wearing-off." Parkinsonism & Related Disorders, vol. 10, no. 4, 2004, pp. 221-6.
Rajput AH, Fenton ME, Di Paolo T, et al. Human brain dopamine metabolism in levodopa-induced dyskinesia and wearing-off. Parkinsonism Relat Disord. 2004;10(4):221-6.
Rajput, A. H., Fenton, M. E., Di Paolo, T., Sitte, H., Pifl, C., & Hornykiewicz, O. (2004). Human brain dopamine metabolism in levodopa-induced dyskinesia and wearing-off. Parkinsonism & Related Disorders, 10(4), 221-6.
Rajput AH, et al. Human Brain Dopamine Metabolism in Levodopa-induced Dyskinesia and Wearing-off. Parkinsonism Relat Disord. 2004;10(4):221-6. PubMed PMID: 15120096.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human brain dopamine metabolism in levodopa-induced dyskinesia and wearing-off. AU - Rajput,Ali H, AU - Fenton,Mark E, AU - Di Paolo,Thérèse, AU - Sitte,Harold, AU - Pifl,Christian, AU - Hornykiewicz,Oleh, PY - 2003/11/03/received PY - 2004/01/22/revised PY - 2004/01/23/accepted PY - 2004/5/4/pubmed PY - 2004/6/30/medline PY - 2004/5/4/entrez SP - 221 EP - 6 JF - Parkinsonism & related disorders JO - Parkinsonism Relat Disord VL - 10 IS - 4 N2 - The objective of this study was to identify dopamine (DA) metabolism pattern in Lewy body Parkinson's disease (PD) patients with dyskinesia (Dysk) only, with wearing-off (WO) only, or no motor complications (NMC) induced by levodopa (LD). DA, homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 3-methoxytyramine (3-MT) were measured individual basal ganglia nuclei of nine PD patients who received LD for 6-18 years. Three patients had only Dysk, three only WO, and three had neither Dysk nor WO. Biochemical measurements in PD brains were compared with four non-neurological control brains from individuals matched for age and post-mortem retrieval time. DA levels in the PD were reduced in the caudate by 87% and putamen by 99%. In the caudates, the HVA/DA molar ratio as an index of DA metabolism was similar in the WO and the Dysk patients. However, in the putamen, the ratio of HVA/DA was significantly higher in the WO compared with the Dysk (p = 0.03)and the NMC (p = 0.04) groups of patients. In the putamen, the DOPAC levels were higher in the WO cases while in the Dysk cases, 3-MT levels were higher. The results suggest that in the WO only cases, the putaminal DA was in large measure metabolized intraneuronally while the DA metabolism in our Dysk only patients was mainly extraneuronal. We conclude that the magnitude and the site (intra vs. extraneuronal) of the synaptic DA metabolism in the putamen plays a significant role in LD-induced Dysk and WO. SN - 1353-8020 UR - https://www.unboundmedicine.com/medline/citation/15120096/Human_brain_dopamine_metabolism_in_levodopa_induced_dyskinesia_and_wearing_off_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1353802004000100 DB - PRIME DP - Unbound Medicine ER -