Monoamine oxidase inhibitors (MAOIs)

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Chapter: Medicinal Chemistry : Antidepressants

Antidepressants - Monoamine oxidase inhibitors (MAOIs) - SYNTHESIS AND DRUG PROFILE - a. Phenelzine (Catron) b. Isocarboxazide C. Tranyl cypromine (Synonym: Parnale) e. Pargyline - Structure, Properties, uses, Synthesis, Assay, Storage, Dosage forms, Dose


SYNTHESIS AND DRUG PROFILE


Monoamine oxidase inhibitors (MAOIs)

Mode of action: MAO is a family of enzymes located in the outer membrane of mitochondria. MAO inhibitors block the intracellular metabolism of biogenic amines, these results in increased amines concentration in the nerve terminals, whereas tricyclic antidepressants and others inhibit the reuptake of NE and serotonin by nerve terminals, this inturn facilitates adrenergic neurotransmission and produces an antidepressant action.


a. Phenelzine (Catron)


Synthesis

Route I. From: 2-Phenyl ethyl alcohol


Route II. From: Acetophenone


Properties and uses: It is a white powder or pearly platelets, insoluble in ethanol and in ether, but freely soluble in water. It is a MAOI with low sedative and antimuscarnic effects, causing weight gain. It is used primarily in the treatment of depression and certain phobic-anxiety states effective in neurotic or typical depressed patients.

Assay: Dissolve the substance in water, add sodium hydrogen carbonate, and 0.05 M iodine VS, close the flask and allow to stand for 90 min. To this add 20 ml of 2 M hydrochloric acid and titrate with 0.1 M sodium thiosulphate, using starch mucilage as an indicator.

Storage: It should be stored in well-closed airtight containers and protected from light.

Dose: The usual dose is 15–30 mg/day, orally 3 times a day.

Dosage forms: Phenelzine tablets B.P.


b. Isocarboxazide


Synthesis

Route I. From: Acetone and diethyl oxalate


Route II. From: Benzyl alcohol


Properties and uses: It exists as white to off-white crystalline powder with slight characteristic odour, stable in dry air. Sparingly soluble in water, well soluble in ethanol, glycerol, or propylene glycol. An MAOI with low sedative and antimuscarnic effects causing weight gain, used in severe depressive state to whom tricyclic antidepressants (TCA) are contraindicated.


C. Tranyl cypromine (Synonym: Parnale)


Synthesis (From: Styrene)


Properties and uses: It is a white or almost white crystalline powder, slightly soluble in ethanol and in ether, but soluble in water. It can be regarded as a ring-closed derivative of amphetamine. It will produce severe hypertensive crisis if taken together with cheese. It is not to be used in cardiovascular disease. It has amphetamine-like action and releases NE centrally. This perhaps accounts for the relative rapidity of action with this drug (in 48 h) in contrast to other MAO inhibitors, which have taken 2–3 weeks. It is used for hospitalized patients with endogenous depression, and who have not responded to other antidepressants. Can be indicated in elderly patients.

Assay: Assayed by nonaqueous titration and the end point determined potentiometrically.

Dose: Usual dose is 20–30 mg/day, orally in the morning and afternoon for 2 weeks.

Dosage forms: Tranyl cypromine tablets B.P.


e. Pargyline


Synthesis


Properties and uses: It possesses hypotensive and stimulant properties. It is recommended for the treatment of hypertension rather than for use in depressed states. It may act through a negative feedback on NE synthesis, and has a long duration of action. Patient receiving pargyline should not receive sympathomimetic amines.



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