DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

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SECTION II
HO
HO
CH 3 O
HO
HO
H
HO H O
HO
C CH 2 NH 2
MAO
HO C C H
MAO
C CH 2 NH 2 HO
HO H OH HO H O
OH
OH
Norepinephrine
DOPGAL
COMT
AR
AD
H
CH 3 O
OH
Normetanephrine
HO C C H HO C C OH
OH H
OH
H
C CH 2 N
OH
Epinephrine
COMT
H
C CH 2 N
OH
Metanephrine
H
CH 3
H
CH 3
NEUROPHARMACOLOGY
CH 3 O
HO
DOPEG
COMT
H OH
C C H
OH H
MOPEG
DOMA
ADH
AR
MAO
CH 3 O
HO
H
C
O
C
H
MAO
OH
MOPGAL
AD
CH 3 O
H
O
HO
C
C
OH
OH
VMA
Figure 8-7. Steps in the metabolic disposition of catecholamines. Norepinephrine and epinephrine are first oxidatively deaminated
to a short lived intermediate (DOPGAL) by monoamine oxidase (MAO). DOPGAL then undergoes further metabolism to more stable
alcohol or acid deaminated metabolites. Aldehyde dehydrogenase (AD) metabolizes DOPGAL to 3,4-dihydroxymandelic acid
(DOMA) while aldehyde reductase (AR) metabolizes DOPGAL to 3,4-dihydroxyphenyl glycol (DOPEG). Under normal circumstances
DOMA is a minor metabolite with DOPEG being the major metabolite produced from norepinephrine and epinephrine. Once
DOPEG leaves the major sites of its formation (sympathetic nerves; adrenal medulla), it is converted to 3-methoxy, 4-hydroxyphenylglycol
(MOPEG) by catechol-0-methyl transferase (COMT). MOPEG is then converted to the unstable aldehyde (MOPGAL) by
alcohol dehydrogenase (ADH) and finally to vanillyl mandelic acid (VMA) by aldehyde dehydrogenase. VMA is the major end product
of norepinephrine and epinephrine metabolism. Another route for the formation of VMA is conversion of norepinephrine or epinephrine
into normetanephrine or metanephrine by COMT either in the adreneal medulla or extraneuronal sites,with subsequent
metabolism to MOPGAL and thence to VMA.