Tranylcypromine (2-PCPA) hydrochloride (SKF-385 HCl), a Monoamine Oxidase inhibitor, is effective in the treatment of major depression, dysthymic disorder, and atypical depression.

MAO-B:7 μM, MAO-A:11.5 μM, LSD1:22.3 μM

Compared with the control group, Tranylcypromine at dosages of 5 mg/kg and 10 mg/kg significantly and gradually increased muscle activity in male rats; however, a 2 mg/kg dosage of Tranylcypromine had no effect. Additionally, Tranylcypromine administered at 10 mg/kg markedly increased the number of copulatory behaviors in male rats.

In bovine aortic endothelial cells, Tranylcypromine (500 μg/mL) markedly inhibits bradykinin-induced release of arachidonic acid. Additionally, Tranylcypromine suppresses the activity of CYP2A6 (IC50: 0.42 μM) and CYP2E1 (IC50: 3 μM) in human liver microsomes (HLMs), inducing type II and cyclopropylbenzene type I difference spectra in HLMs. Nicotine metabolism mediated by CYP2A6 in HLMs is completely inhibited by R-(+)-Tranylcypromine (Ki: 0.05 μM), (±)-Tranylcypromine (Ki: 0.08 μM), and S-(-)-Tranylcypromine (Ki: 2.0 μM).

PDE activity is determined with some modifications. The assay mixture contain 50 mM Tris (pH 7.4), 5 mM MgCl2, 0.5 μM cAMP or cGMP, and [3H]cAMP or [3H]cGMP (about 30,000 cpm/assay), the indicated concentration of the inhibitor and an aliquot of the enzyme solution at a final assay volume of 200 μL. Stock solutions of the compounds are diluted 1:100 (v/v) in the Tris buffer mentioned above; appropriate dilutions are prepared in 1% (v/v) DMSO/Tris buffer, which are diluted 1:2 (v/v) in the assays to obtain the desired final concentrations of the inhibitors at a DMSO concentration of 0.5% (v/v). DMSO itself affected none of the PDE activities. After preincubation for 5 min at 37°C, the reaction is started by the addition of substrate (cAMP or cGMP) and the assays are incubated for further 15 min at 37°C. Then 50 μL of 0.2 N HCl is added to stop the reaction and the assays are left on ice for about 10 min. Following incubation with 25 μg of 5′-nucleotidase (Crotalus atrox snake venom) for 10 min at 37°C, the assays are loaded on QAE Sephadex A-25 (1 mL of bed volume in Poly-Prep chromatography columns). The columns are eluted with 2 mL of 30 mM ammonium formate (pH 6.0) and the eluate is counted for radioactivity. Results are corrected for blank values (measured in the presence of denatured protein) that are below 5% of total radioactivity. The amount of cyclic nucleotides hydrolyzed did not exceed 30% of the original substrate concentration[3].