Tranylcypromine

Chemical properties

white to light beige powder or chunks

The Uses of Tranylcypromine

As with the MAO inhibitor drugs described above, tranylcypromine is also used for depressions that do not respond to other drugs.

The Uses of Tranylcypromine

Non-selective MAO-A/B inhibitor

The Uses of Tranylcypromine

Antidepressant;MAO inhibitor

What are the applications of Application

trans 2-Phenylcyclopropylamine Hydrochloride is a non-selective inhibitor of MAO

Definition

ChEBI: (1R,2S)-tranylcypromine hydrochloride is a hydrochloride obtained by combining (1R,2S)-tranylcypromine with one equivalent of hydrochloric acid. It contains a (1R,2S)-tranylcypromine(1+). It is an enantiomer of a (1S,2R)-tranylcypromine hydrochloride.

General Description

A cell-permeable phenylcyclopropylamine that inhibits the monoamine oxidase and histone demethylase activities, respectively, of MAO A/B (K_i = 101.9 and 16.0 M, respectively) and LSD1/2 (K_i = 242.7 and 180.0 M, respectively), four members of a flavin-dependent amine oxidase family enzymes, by a covalent adduct formation with the enzyme-bound FAD. In addition to preventing LSD1-CoREST (Corepressor of RE1-Silencing Transcription factor) complex-mediated H3K4 demethylation (IC₅₀<2 M), TCP also inhibits LSD1-HCF-1 (Host Cell Factor-1) complex-mediated H3K9 demethylase activity, which is demonstrated to be an essential mechanism for the replication and latent infection of the α-herpesviruses HSV and VZV. The combined treatment of 2 M TCP and 10 M CHIR99061 is reported to enable the reprogramming of Oct4/Klf4-transduced primary HNEKs (Human Neonatal Epidermal Keratinocytes) into iPS (induced Pluripotent Stem) cells, albeit at a 100-time lower efficiency as seen in cultures transduced with 4-TFs (Oct44, Klf4, Sox2, and c-Myc).

Biological Activity

Irreversible inhibitor of lysine-specific demethylase 1 (LSD1/BHC110) and monoamine oxidase (MAO) (K i values are 242, 102 and 16 μ M for LSD1, MAO-A and MAO-B respectively). Inhibits histone demethylation.

Clinical Use

MAOI antidepressant

Synthesis

Tranylcypromine, (?à)-trans-2-phenylcyclopropylamine (7.2.10), differs from the drugs described above in that it is not a derivative of hydrazine. It is synthesized from the ethyl ester of 2-phenylcyclopropan carboxylic acid (7.2.7), which is synthesized by the reaction of styrene with ethyl diazoacetate. 2-phenylcyclopropancarboxylic acid ethyl ester (7.2.7) is hydrolyzed by alkali to 2-phenylcyclopropancarboxylic acid (7.2.8) and the trans-isomer is separated for further reactions. The reaction of the trans-isomer with thionyl chloride gives trans-2-phenylcyclopropancarboxylic acid chloride (7.2.9), which upon reaction with sodium azide gives the respective acid azide, which undergoes Curtius rearrangement to the transcyclopropylamine (7.2.10) [48,49].

Drug interactions

Potentially hazardous interactions with other drugs
Alcohol: some alcoholic and dealcoholised drinks contain tyramine which can cause hypertensive crisis.
Alpha-blockers: enhanced hypotensive effect; avoid with indoramin.
Analgesics: CNS excitation or depression with pethidine, other opioids and nefopam - avoid; increased risk of serotonergic effects and convulsions with tramadol - avoid.
Antibacterials: increased risk of hypertension and CNS excitation with linezolid and tedizolid - avoid for at least 2 weeks after stopping MAOIs.
Antidepressants: enhancement of CNS effects and toxicity. Care with all antidepressants including drug free periods when changing therapies.
Antidiabetics: possibly enhanced hypoglycaemic effect.
Antiepileptics: antagonism of anticonvulsant effect; avoid carbamazepine with or within 2 weeks of MAOIs.
Antihypertensives: enhanced hypotensive effect.
Antimalarials: avoid with artemether/lumefantrine and piperaquine with artenimol.
Antipsychotics: effects enhanced by clozapine.
Anxiolytics: avoid buspirone with or within 2 weeks of MAOIs.
Atomoxetine: avoid concomitant use and for 2 weeks after use; increased risk of convulsions.
Bupropion: avoid with or for 2 weeks after MAOIs.
Dapoxetine: risk of hypertensive crisis - avoid.
Diuretics: enhanced hypotensive effect; avoid with indoramin.
Dopaminergics: avoid with entacapone, safinamide and tolcapone; hypertensive crisis with levodopa and rasagiline - avoid for at least 2 weeks after stopping MAOI; hypotension with selegiline.
5HT1 agonist: risk of CNS toxicity with sumatriptan, rizatriptan and zolmitriptan - avoid sumatriptan and rizatriptan for 2 weeks after MAOI.
Metaraminol: risk of hypertensive crisis - avoid for at least 2 weeks after stopping MAOIs.
Methyldopa: avoid concomitant use.
Opicapone: avoid concomitant use.
Sympathomimetics: hypertensive crisis with sympathomimetics - avoid.
Tetrabenazine: risk of CNS excitation and hypertension avoid.

Metabolism

Tranylcypromine undergoes considerable hepatic metabolism, including breakdown of the side chain and probably conjugation. Excretion is renal mainly as metabolites.

storage

room temperature (desiccate)