Active ingredient: Maprotiline - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Antidepressants
• Adrenergic Uptake Inhibitors

Dosage Forms

• Tablet (10, 25, 50, and 75mg film coated)

Brands / Synonyms

Deprilept; Ludiomil; Maprotilina [Inn-Spanish]; Maprotiline; Maprotiline Hcl; Maprotiline [Usan:Ban:Inn]; Maprotilinum [Inn-Latin]; Maprotylina; Maprotylina [Polish]; Psymion

Indications

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.

Pharmacology

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.

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

Completely absorbed following oral administration

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.

Biotrnasformation / Drug Metabolism

Hepatic. Maprotiline is metabolized by N-demethylation, deamination, aliphatic and aromatic hydroxylations and by formation of aromatic methoxy derivatives.

Contraindications

Maprotiline is contraindicated in patients with known or suspected convulsive disorders, since it is known to lower the seizure threshold. It is also contraindicated in patients with a history of hypersensitivity to the drug, and in those with existing severe hepatic or renal damage or a history of severe blood dyscrasias. Patients with narrow angle glaucoma, or with urinary retention (i.e., due to prostatic disease) should not receive maprotiline because of its anticholinergic properties. Maprotiline is contraindicated during the acute recovery phase following myocardial infarction in the presence of acute congestive heart failure, and in patients with conduction defects. Maprotiline should not be given in conjunction with, or within 14 days of treatment with a MAO inhibitor. Combined therapy of this type could lead to the appearance of serious interactions such as hyperpyrexia, tremors, generalized clonic convulsions, delirium and possible death. Maprotiline should not be employed, or should be withdrawn, in cases of acute poisoning with alcohol, hypnotics, analgesics or psychotropic drugs. Maptrotiline should not be used by children.

Drug Interactions

May interact with the following: alcoholic beverages, barbiturates, and other CNS depressants (response may be exaggerated), adrenergic neuron blocking drugs (maprotiline may diminish or abolish the antihypertensive effects of these drugs), beta-blockers subject to substantial biotransformation, such as propranolol (concomitant use may increase the plasma concentrations of maprotiline), sympathomimetic drugs such as noradrenaline, adrenaline, and methylphenidate (maprotiline may potentiate the cardiovascular effects of these drugs), and maprotiline may also potentiate the effects of anticholinergic drugs (atropine, biperiden) and levodopa. Drugs that activate hepatic microsomal enzymes, such as barbiturates, phenytoin, oral contraceptives and carbamazepine, may accelerate the metabolism of maprotiline resulting in decreased antidepressant efficacy. Concomitant administration of phenytoin and maprotiline may increase serum phenytoin levels resulting in manifestation of the latter's side-effects. Concomitant treatment with maprotiline and major tranquilizers may result in increased plasma levels of maprotiline, a lowered convulsion threshold, and seizures. The combination of maprotiline and benzodiazepines may cause increased sedation. Maprotiline should not be administered for a period of at least 14 days after the discontinuation of treatment with MAO-inhibitors due to the potential of severe interactions. Concurrent use of parenteral magnesium sulfate and maprotiline may result in serious potentiation of CNS depressant effects.