Proadifen (hydrochloride)

Proadifen (SKF-525A) hydrochloride is a non-competitive Cytochrome P450 inhibitor with an IC₅₀ value of 19 μM. Proadifen hydrochloride reduces monoamine oxidase A (MAO-A) activity and reverses the antidepressantlike behavioral effect of Imipramine (HY-B1490A) and Desipramine (HY-B1272A) in rats. Proadifen hydrochloride also reduces N, N-dimethyltryptamine (DMT) metabolism in liver microsomes and inhibits N-demethylationand Acridone (HY-W007771) formation. Proadifen hydrochloride augments Lipopolysaccharide (LPS) (HY-D1056)-induced fever and exacerbates Prostaglandin E2 (PGE2) (HY-101952) levels in the rat. Proadifen hydrochloride is promising for research of metabolism-related deseases, ovarian carcinoma, inflammation and dopamine neurons-related deseases^{[1][2][3][4][5][6]}. In Vitro:Proadifen hydrochloride (10 mM, 60 min) has a larger inhibition on N, N-dimethyltryptamine (DMT) metabolism compared to Quinidine (HY-B1751H) (2.1-fold increase in half-life) in liver microsomes^[2].
Proadifen hydrochloride (8 μM, 2 min) inhibits the formation of Acridone (HY-W007771) with 50% inhibition in rat hepatic cytosolic fraction^[3].
Proadifen hydrochloride (11.09-79.86 μM, 24 h and 48 h) combined with Cisplatin (CDDP) (HY-17394) inhibits cell proliferation, metabolic activity, the upregulation of MRP1, MRP2, CYP3A4 proteins levels induced by CDDP (HY-17394) and attenuates cell cycle arrest, also downregulates the expression of Bcl-XL, Bcl-2, survivin, but increases PARP cleavage in A2780 and A2780cis ovarian cancer cells^[6].
In Vivo:Proadifen hydrochloride (25 mg/kg, i.p., three times) inhibits the excitability of 5-HT neurons, Corticosterone (HY-B1618) might play a key role in the Proadifen hydrochloride-induced inhibition of 5-HT neurons in rats^[1][4].
Proadifen hydrochloride (15 mg/kg, i.p., a single dose for 3 h) exacerbates PGE2 levels elevated by LPS in rats^[5].