A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Elavil Pharmacology, Pharmacokinetics, Studies, Metabolism - Amitriptyline
Elavil Pharmacology, Pharmacokinetics, Studies, Metabolism - Amitriptyline
CLINICAL PHARMACOLOGY
Amitriptyline HCl is an antidepressant
with sedative effects. Its
mechanism of action in man
is not known. It is not a monoamine
oxidase inhibitor and it does
not act primarily by stimulation
of the central nervous
system.
Amitriptyline inhibits the membrane
pump mechanism
responsible for uptake of norepinephrine
and serotonin in adrenergic
and serotonergic neurons. Pharmacologically this action
may potentiate or prolong
neuronal activity since reuptake of these biogenic
amines is important physiologically in terminating transmitting activity.
This interference with
the reuptake of norepinephrine
and/or serotonin is believed
by some to underlie the antidepressant activity of amitriptyline.
Metabolism
Studies in man following oral
administration of 14C-labeled
drug indicated that amitriptyline is rapidly absorbed and metabolized.
Radioactivity of the plasma
was practically negligible, although significant amounts of radioactivity
appeared in the urine by 4 to
6 hours and one-half to one-third of the drug
was excreted within 24 hours.
Amitriptyline is metabolized by N-demethylation and bridge
hydroxylation in man, rabbit, and rat. Virtually the entire
dose is excreted as glucuronide
or sulfate conjugate
of metabolites, with little unchanged drug
appearing in the urine. Other metabolic pathways may be involved.
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