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
Tofranil Pharmacology, Pharmacokinetics, Studies, Metabolism - Imipramine
Tofranil Pharmacology, Pharmacokinetics, Studies, Metabolism - Imipramine
CLINICAL PHARMACOLOGY
The mechanism of
action of imipramine
hydrochloride
is not definitely known. However, it does not act
primarily by stimulation
of the central nervous system. The clinical
effect is hypothesized
as being due to potentiation of adrenergic
synapses by blocking
uptake of norepinephrine
at nerve endings. The
mode of action
of the drug in controlling
childhood enuresis
is thought to be apart from its antidepressant
effect.
ANIMAL PHARMACOLOGY AND TOXICOLOGY
Acute
Oral LD50 ranges are as follows:
Rat: 355 to 682 mg/kg
Dog: 100 to 215 mg/kg
Depending on the dosage
in both species, toxic
signs proceeded progressively from depression,
irregular respiration
and ataxia to convulsions
and death.
Reproduction/Teratogenic
The overall evaluation
may be summed up in the following manner:
Oral: Independent studies in three species
(rat, mouse and rabbit) revealed that when imipramine is administered
orally in doses up to approximately 2 1/2 times the maximum
human dose
in the first 2 species and up to 25 times the maximum
human dose
in the third species,
the drug is essentially free from teratogenic
potential. In the three species
studied, only one instance of fetal
abnormality occurred
(in the rabbit) and in that study there was likewise an abnormality
in the control group.
However, evidence does exist from the rat
studies that some systemic
and embryotoxic potential is demonstrable. This is manifested by
reduced litter size,
a slight increase in the stillborn
rate and a reduction
in the mean birth weight.
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