Maprotiline action

Older tricyclic antidepressants are set in italics. The specificity of action of tricyclic antidepressants (in particular of amitritpyline, imipmmine, doxepine, noitriptyline, maprotiline) is limited because at therapeutic levels ihese drugs also block receptors (H t-histamine, a,-adrenergic, muscarinic). 

Maprotiline, a tetracyclic compound, largely resembles tricyclic agents in terms of its pharmacological and clinical actions. Mianserine also possesses a tetracyclic structure, but differs insofar as it increases intrasyn-aptic concentrations of norepinephrine... 

Amphetamine and cocaine also increase noradrenaline release and a number of drugs with mainly noradrenergic actions can also cause a hyperactive delirium. These include ephedrine, phenylpropanolamine, aminophylline, maprotiline and monoamine oxidase inhibitors (Hollister, 1986). 

Although its mechanism of action is similar to that of desipramine and maprotiline, reboxetine is not a TCA, and, in contrast, does not inhibit electrically excitable membranes. For this reason, overdose of reboxetine should not carry a significant risk of cardiotoxicity or seizures. Although a distinct advantage, the aforementioned is based on preclinical data because there is minimal clinical experience with overdoses of this drug. 

The actions of amoxapine and maprotiline resemble those of TCAs such as desipramine. Both are potent NET inhibitors and less potent SERT inhibitors. In addition, both possess anticholinergic properties. Unlike the TCAs or other antidepressants, amoxapine is a moderate inhibitor of the postsynaptic D2 receptor. As such, amoxapine possesses some antipsychotic properties. 

The newer agents that may have actions that are novel or atypical include maprotiline, amoxapine, fluoxetine, trazodone, bupropion, mianserin, and alprazolam. 

Maprotiline (a tetracyclic drug) is most like desipramine in terms of its potent norepinephrine uptake inhibition. Like the latter drug, it has fewer sedative and antimuscarinic actions than the older tricyclics. 

None of the newer antidepressants have been shown to be more effective overall than the tricyclics with which they have been compared. Solid evidence to support a claim of more rapid onset of action has been difficult to obtain. Amoxapine and maprotiline seem to have as many sedative and autonomic actions as most tricyclics more recently introduced antidepressants such as bupropion and venlafaxine have fewer, although nefazodone and mirtazapine are very sedating. Amoxapine and maprotiline are at least as dangerous as the tricyclics when taken in overdoses the other newer agents seem to be safer. 

Forrest WA. Maprotiline (Ludiomil) in depression a multicentre assessment of onset of action, efficacy and tolerability. J Int Med Res 1977 5(Suppl 4) 116-21. 

Increased depressive effects when taken with other CNS depressants Cimetidine raises loflazepate plasma levels Rapid dose reduction or discontinuation of loflazepate during concomitant use with tetracyclic antidepressants such as maprotiline may result in convulsive seizures, possibly due to the loss of anticonvulsant actions that suppress the pro-convulsant actions of tetracyclic antidepressants... 

Bupropion, reboxetine, nortriptyline, desipramine, maprotiline, atomoxetine (all potentially po A/erful enhancers of noradrenergic action, but observe for activation of bipolar disorder and suicidal ideation)... 

HT, antagonist with antidepressant activity (123) it binds with high affinity (if < 10 nM) at 5-HT, receptors (124). Hence, trazodone (24), nefazodone (16), and mianserin (27) represent atypical antidepressants that have in common a high affinity for S-HTgA receptors and S-HTg antagonist action. It might be noted that certain tricyclic antidepressants also bind at 5-HT, receptors imipramine (11), desipramine (6), nortriptyline (17), and maprotiline (13), for example, bind with submicromolar Ki values (124) (Table 8.6). 

Mechanisms of action vary Amoxapine and maprotiline block NE reuptake nefazodone (weak) and trazodone block 5HT reuptake, but both drugs also act as antagonists at certain... 

Maprotiline is chemieally similar to the tricyclic drug desipramine except that it has a tetra-cyelic structure. Maprotiline is almost equivalent to desipramine in terms of its sedative and muscarinic receptor blocking actions but has caused seizures at the top of its recommended dose range. Both drugs act selectively to block the reuptake of norepinephrine. The answer is (D). 

Maprotiline exhibits the highest affinity and selectivity for the NE transporter (Fig. 21.6). Its antidepressant mechanism of action is similar to that of desipramine, with an onset of action of up to 2 to 3 weeks. 

Mianserin and maprotiline are tetracyclic antidepressants, which have actions similar to those of the tricyclie antidepressants. However, while the tetracyclics are more sedating, their antimusearinic effects are less marked. Maprotiline inhibits the leuptake of noradrenaline (norepinephrine) and has weak affinity for eentral adrenergic (aj) receptors. Mianserin does not prevent the peripheral reuptake of noradrenaline it blocks presynaptic adrenergic (a2) receptors and increases the turnover of hrain noradrenaline. It is also an antagonist of serotonin receptors in some parts of the brain. 

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