Drug/Small Molecule:

maprotiline

A bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use. PubChem (source: Drug Bank)

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. (source: Drug Bank)

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. (source: Drug Bank)

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 re-uptake 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. (source: Drug Bank)

Take without regard to meals. Limit caffeine intake. (source: Drug Bank)

Hepatic. Maprotiline is metabolized by N-demethylation, deamination, aliphatic and aromatic hydroxylations and by formation of aromatic methoxy derivatives. (source: Drug Bank)

88% (source: Drug Bank)

Completely absorbed following oral administration (source: Drug Bank)

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. (source: Drug Bank)

CNCCCC12CCC(c3c1cccc3)c4c2cccc4 (source: Drug Bank)