Document Detail


Potent in vivo but not in vitro inhibition of monoamine oxidase by 3-chloro-alpha-phenylpyrazinemethanol.
MedLine Citation:
PMID:  1304317     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
3-Chloro-alpha-phenylpyrazinemethanol (3-CPM) inhibited monoamine oxidase (MAO) types A and B in vivo in mouse brain, heart and liver. The inhibition was dose-dependent at doses of 0.3-32 mg/kg i.p. and occurred within 1 h after the compound was injected. 3-CPM was a very weak inhibitor of mouse brain mitochondrial MAO activity in vitro, even when preincubated with the enzyme; MAO-A was inhibited only about 50% at a high concentration of 3-CPM (1 mM), and MAO-B was inhibited even less. After a 10 mg/kg i.p. dose of 3-CPM in mice, both MAO-A and MAO-B were inhibited at day 1, but activity had largely recovered within a few days in brain, liver and heart. 3-CPM at doses of 1, 3, 10 and 32 mg/kg i.p. caused dose-dependent antagonism of the depletion of striatal dopamine and of cortical norepinephrine by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. 3-CPM is therefore a potent inhibitor of MAO-A and of MAO-B in mice in vivo despite its weak effect on the enzyme in vitro. A metabolite of the drug may be involved in the in vivo effects.
Authors:
R W Fuller; S K Hemrick-Luecke; J S Ward
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Neurochemistry international     Volume:  20     ISSN:  0197-0186     ISO Abbreviation:  Neurochem. Int.     Publication Date:  1992 Jan 
Date Detail:
Created Date:  1993-07-07     Completed Date:  1993-07-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  37-42     Citation Subset:  IM    
Affiliation:
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
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MeSH Terms
Descriptor/Qualifier:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
Animals
Benzyl Alcohols / pharmacology*
Brain / enzymology*
Corpus Striatum / drug effects,  metabolism
Dopamine / metabolism
Frontal Lobe / drug effects,  metabolism
Isoenzymes / antagonists & inhibitors*
Kinetics
Liver / enzymology
Male
Mice
Mice, Inbred Strains
Monoamine Oxidase / metabolism*
Monoamine Oxidase Inhibitors / pharmacology*
Myocardium / enzymology
Norepinephrine / metabolism
Pyrazines / pharmacology*
Chemical
Reg. No./Substance:
0/Benzyl Alcohols; 0/Isoenzymes; 0/Monoamine Oxidase Inhibitors; 0/Pyrazines; 121246-85-3/3-chloro-alpha-phenylpyrazinemethanol; 28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 51-41-2/Norepinephrine; EC 1.4.3.4/Monoamine Oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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