Maprotiline

277.4

277.40

233-599-4

2U1W68TROF

DTXSID7045029

N - Nervous system

2921499090

12

5.1

Solid

0.9801 (rough estimate)

93 °C

410.26°C (rough estimate)

187.7ºC

1.4900 (estimate)

H2O: Slightly soluble

LD50 oral in rat: 760mg/kg

164.2 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|163.8 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated]

III

6.1(b)

3249

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.

88%

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.

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.

A structurally and mechanistically diverse group of drugs that are not tricyclics or monoamine oxidase inhibitors. The most clinically important appear to act selectively on serotonergic systems, especially by inhibiting serotonin reuptake. (See all compounds classified as Antidepressive Agents, Second-Generation.)|Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin. (See all compounds classified as Adrenergic Uptake Inhibitors.)

Slowly, but completely absorbed from the GI tract following oral administration.|Approximately 60% of a single orally administered dose is excreted in urine as conjugated metabolites within 21 days; 30% is eliminated in feces.|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.

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.|Maprotiline has known human metabolites that include 2-hydroxy-maprotiline, 3-hydroxy-maprotiline, and desmethylmaprotiline.

Average ~ 51 hours (range: 27-58 hours)

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.

Ba-34,276

Pharmaceuticals