Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively. Tranylcypromine is a propylamine formed from the cyclization of amphetamines side chain; therefore, it is classified as a substituted amphetamine. Medical uses
Tranylcypromine is used to treat major depressive disorder, including atypical depression, especially when there is an anxiety component, typically as a second-line treatment. It is also used in depression that is not responsive to reuptake inhibitor antidepressants, such as the SSRIs, TCAs, or bupropion.Systematic reviews and meta-analyses have reported that tranylcypromine is significantly more effective in the treatment of depression than placebo and has efficacy over placebo similar to that of other antidepressants such as tricyclic antidepressants. Contraindications
Contraindications include:
Porphyria
Cardiovascular or cerebrovascular disease
Pheochromocytoma
Tyramine, found in several foods, is metabolized by MAO. Ingestion and absorption of tyramine causes extensive release of norepinephrine, which can rapidly increase blood pressure to the point of causing hypertensive crisis. Concomitant use of serotonin-enhancing drugs, including SSRIs, serotonergic TCAs, dextromethorphan, and meperidine may cause serotonin syndrome. Concomitant use of MRAs, including fenfluramine, amphetamine, and pseudoephedrine may cause toxicity via serotonin syndrome or hypertensive crisis. L-DOPA given without carbidopa may cause hypertensive crisis. Dietary restrictions
Tyramine is a common component in many foods, and is normally rapidly metabolized by MAO-A.
It is also used with octreotide for hepatorenal syndrome; the proposed mechanism is constriction of splanchnic vessels and dilation of renal vasculature. Studies have not been sufficiently well conducted to show a clear place for midodrine. Contraindications
Midodrine is contraindicated in patients with severe organic heart disease, acute kidney disease, urinary retention, pheochromocytoma or thyrotoxicosis. Midodrine should not be used in patients with persistent and excessive supine hypertension. Side effects
Headache, feeling of pressure/fullness in the head, vasodilation/flushing face, scalp tingling, confusion/thinking abnormality, dry mouth, nervousness/anxiety and rash. Pharmacology
Mechanism of action
Midodrine is a prodrug which forms an active metabolite, desglymidodrine, which is an α1-receptor agonist and exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure. Desglymidodrine does not stimulate cardiac beta-adrenergic receptors. Desglymidodrine diffuses poorly across the blood–brain barrier, and is therefore not associated with effects on the central nervous system. Pharmacokinetics
After oral administration, midodrine is rapidly absorbed. The plasma levels of the prodrug peak after about half an hour, and decline with a half-life of approximately 25 minutes, while the metabolite reaches peak blood concentrations about 1 to 2 hours after a dose of midodrine and has a half-life of about 3 to 4 hours. The absolute bioavailability of midodrine (measured as desglymidodrine) is 93%. Chemistry
Midodrine is an odorless, white, crystalline powder, soluble in water and sparingly soluble in methanol.