Investigation of the enzymology and pharmacology of novel substrates and inhibitors of dopamine beta-monooxygenase
Dopamine beta-monooxygenase (DBM) was shown to catalyze the selenoxidation of 2-(phenylseleno)ethylamines, selenium-containing analogues of dopamine, by the normal monooxygenase pathway. The compounds 2-(phenylseleno)-ethylamine (PAESe), 2-(4'-hydroxyphenylseleno)ethylamine (pOH PAESe), and 1-(phenylseleno)-2-propylamine (Me PAESe) were synthesized and fully characterized as DBM substrates. Two other classes of compounds were investigated as potential alternate substrates for DBM. The possibility of stereoselective sulfonylation of 2-(phenylsulfenyl)- ethylamine (PAESO) was considered. A unique class of compounds, 2-(phenylthio)ethanols were designed and synthesized as DBM substrates but were found to be a novel class of potent competitive inhibitors of DBM with respect to tyramine. Preliminary experiments were also performed in an effort to demonstrate that the potent antihypertensive and indirect-acting sympathomimetic activity of 2-(phenylthio)ethylamine (PAES) was a result of DBM-oxygenation of this compound in vivo. The specific reserpine-sensitive uptake of (/sup 3/H)-norepinephrine into rat brain synaptosomes was demonstrated as was the synaptosomal conversion of (/sup 3/H)-dopamine to (/sup 3/H)-norepinephrine.
- Research Organization:
- Georgia Inst. of Tech., Atlanta (USA)
- OSTI ID:
- 6411829
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL PATHWAYS
BODY
BRAIN
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DOPAMINE
DRUGS
ENZYME INHIBITORS
ENZYMES
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
NERVES
NERVOUS SYSTEM
NEUROREGULATORS
NORADRENALINE
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGENASES
PHENOLS
POLYPHENOLS
RATS
REACTION KINETICS
RODENTS
SUBSTRATES
SYMPATHOMIMETICS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES