Indication |
For treatment of depression, including the depressed phase of
bipolar depression, psychotic depression, and involutional melancholia,
and may also be helpful in treating certain patients suffering severe
depressive neurosis. |
Pharmacodynamics |
Maprotiline is a tetracyclic antidepressant. Although its main
therapeutic use is in the treatment of depression, it has also been
shown to exert a sedative effect on the anxiety component that often
accompanies depression. In one sleep study, it was shown that
maprotiline increases the duration of the REM sleep phase in depressed
patients, compared to imipramine which reduced the REM sleep phase.
Maprotiline is a strong inhibitor of noradrenaline reuptake in the brain
and peripheral tissues, however it is worthy to note that it is a weak
inhibitor of serotonergic uptake. In addition, it displays strong
antihistaminic action (which may explain its sedative effects) as well
as weak anticholinergic action. Maprotiline also has lower alpha
adrenergic blocking activity than amitriptyline. |
Mechanism of action |
Maprotiline exerts its antidepressant action by inhibition of
presynaptic uptake of catecholamines, thereby increasing their
concentration at the synaptic clefts of the brain. In single doses, the
effect of maprotiline on the EEG revealed a rise in the alpha-wave
density, a reduction of the alpha-wave frequency and an increase in the
alpha-wave amplitude. However, as with other tricyclic antidepressants,
maprotiline lowers the convulsive threshold. Maprotiline acts as an
antagonist at central presynaptic α2-adrenergic inhibitory
autoreceptors and hetero-receptors, an action that is postulated to
result in an increase in central noradrenergic and serotonergic
activity. Maprotiline is also a moderate peripheral α1
adrenergic antagonist, which may explain the occasional orthostatic
hypotension reported in association with its use. Maprotiline also
inhibits the amine transporter, delaying the reuptake of noradrenaline
and norepinephrine. Lastly, maprotiline is a strong inhibitor of the
histamine H1 receptor, which explains its sedative actions. |
Absorption |
Slowly, but completely absorbed from the GI tract following oral administration. |
Volume of distribution |
Maprotiline and its metabolites may be detected in the lungs,
liver, brain, and kidneys; lower concentrations may be found in the
adrenal glands, heart and muscle. Maprotiline is readily distributed
into breast milk to similar concentrations as those in maternal blood. |
Protein binding |
88% |
Metabolism |
Hepatic. Maprotiline is metabolized by N-demethylation,
deamination, aliphatic and aromatic hydroxylations and by formation of
aromatic methoxy derivatives. It is slowly metabolized primarily to
desmethylmaprotiline, a pharmacologically active metabolite.
Desmethylmaprotiline may undergo further metabolism to maprotiline-N-oxide. |
Route of elimination |
Approximately 60% of a single orally administered dose is excreted
in urine as conjugated metabolites within 21 days; 30% is eliminated in
feces. |
Half life |
Average ~ 51 hours (range: 27-58 hours) |
Clearance |
Not Available |
Toxicity |
LD50=~900 mg/kg (Orally in rats); LD50=90
mg/kg (Orally in women); Signs of overdose include motor unrest,
muscular twitching and rigidity, tremor, ataxia, convulsions,
hyperpyrexia, vertigo, mydriasis, vomiting, cyanosis, hypotension,
shock, tachycardia, cardiac arrhythmias, impaired cardiac conduction,
respiratory depression, and disturbances of consciousness up to deep
coma. |
Comments
Post a Comment