Maprotiline Norepinephrine

The answer is c. (Hardman, p 436.) The tricyclics and second-generation antidepressants act by blocking serotonin or norepinephrine uptake into the presynaptic terminal. Fluoxetine selectively inhibits serotonin uptake with minimal effects on norepinephrine uptake. Protriptyline, maprotiline, desipramine, and amoxapine have greater effect on norepinephrine uptake... 

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... 

Pharmacology Tetracyclics enhance central noradrenergic and serotonergic activity. They do not inhibit monoamine oxidase. Although maprotiline and mirtazapine are in the same chemical class, they each affect different neurotransmitters and thus have different side effect profiles. Maprotiline primarily acts by blocking reuptake of norepinephrine at nerve endings. 

Maprotiline and amoxapine are selective norepinephrine uptake inhibitors. They share most of the properties of the tricyclic antidepressants. Maprotiline has less sedating effect than mianserin and it is more epileptogenic than any other antidepressant. It shows considerable cardiotoxicity when taken in overdose. 

Maprotiline (bupropion) NET > SERT inhibition (amoxapine, maprotiline) t increased release of norepinephrine, 5-HT (mirtazapine) but no effect on 5-HT (bupropion) amoxapine and maprotiline resemble TCAs (mirtazapine) amoxapine and maprotiline rarely used bupropion) sedation and weight gain (mirtazepine) Interactions CYP2D6 inhibitor (bupropion)... 

Maprotiline [Ludiomil] Moderate inhibition of norepinephrine reuptake Sedating useful in agitation Possibility of seizures overdoses lethal long half-life... 

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. 

Since dopamine is inactivated by norepinephrine reuptake in frontal cortex, wrhich largely lacks dopamine transporters, maprotiline can thus increase dopamine neurotransmission in this part of the brain... 

Reuptake of norepinephrine inhibited by TCAs, amoxapine, maprotiline, atomoxetine... 

Maprotiline selectively inhibits the reuptake of norepinephrine at the neuronal membrane. 

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). 

Entacapone and imipramine did not interact adversely in a single-dose study. Similarly, tolcapone and desipramine did not interact adversely. Nevertheless, the manufacturers of entacapone and tolcapone recommend caution if they are used with tricyclic antidepressants or other drugs that inhibit noradrenaline (norepinephrine) uptake, such as maprotiline or venlafaxine. 

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. 

The pressor (increased blood pressure) responses to tyramine and noradrenaline (norepinephrine) in depressed patients remained virtually unchanged after 14 days of treatment with mianserin 60 mg daily.In 5 healthy subjects taking maprotiline the pressor response to tyramine was reduced threefold while the noradrenaline response remained unchanged. ... 

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