1H NMR probe for in situ monitoring of dopamine metabolism and its application to inhibitor screening.
Dopamine (DA) is a monoamine neurotransmitter that plays important roles in the brain, and whose levels in the brain are associated with several neurological and psychiatric disorders. Therefore, DA metabolism inhibitors have been used as therapeutic agents. Here, we report a (1)H NMR probe for the in situ analysis of DA metabolism, and its application to DA inhibitor screening. We designed doubly (13)C-labeled DA ((13)C(2)-DA) as the probe. The combination of the (13)C(2)-DA and (1)H-{(13)C-(13)C'} NMR technique allowed the selective and thus in situ monitoring of DA metabolism. Using (13)C(2)-DA, we successfully measured the efficacies of different inhibitors in a tissue sample, allowing us to improve the in situ inhibitory efficacy of the known DA metabolism inhibitor, clorgyline.
INAMORI Frontier Research Center, Kyushu University, Nishi-ku, Fukuoka, Japan.
Ryosuke
R
Ueki
Koya
K
Yamaguchi
Hiroshi
H
Nonaka
Shinsuke
S
Sando
D000818:Animals; D002247:Carbon Isotopes / Q000737:chemistry / Q000378:metabolism; D004298:Dopamine / Q000737:chemistry / Q000378:metabolism*; D015259:Dopamine Agents / Q000737:chemistry / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism
D002247:Carbon Isotopes; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D008995:Monoamine Oxidase; D004298:Dopamine