Piribedil hydrochloride can be used in the parkinson's disease, circulatory disorders, cancers research. Piribedil hydrochloride inhibits MLL1 methyltransferase activity with EC50 value of 0.18 μM. Piribedil hydrochloride is a potent and orally active agonist of dopamine D2 and dopamine D3 as well as the antagonist of α2-adrenoceptors [1] [2] [3] [4].
In vitro
Piribedil hydrochloride (0-160 μM, 7 days) specifically inhibits MLL1 methyltransferase activity and selectively suppresses MLL-r cell proliferation [4]. Piribedil hydrochloride (0-160 μM, 4 days) selectively decreases the H3K4 methylation in MLL-r cells (THP-1 and MV4;11), by disturbing the MLL1-WDR5 interaction [4]. Piribedil hydrochloride (0-160 μM, 4 days) induces cell-cycle arrest, apoptosis and differentiation in MLL-r cells (THP-1 and MV4;11) [4]. Cell Proliferation Assay [4] Cell Line: MLL-r AML cells (THP-1 and MV4;11), non-MLL leukemia cell line (K562) Concentration: 0, 20, 40, 80 and 160 μM Incubation Time: 0-7 days Result: Inhibited the growth rate of the THP-1 and MV4;11 cells in a time-dependent manner. Western Blot Analysis [4] Cell Line: THP-1 and MV4;11 cells Concentration: 0, 20, 40, 80 and 160 μM Incubation Time: 4 days Result: Decreased the levels of H3K4me2 and H3K4me3 without affecting the methylation of other histones, such as H3K79, H3K36 and H3K27.
In vivo
Piribedil hydrochloride (intraperitoneal injection, 5, 15, 40 mg/kg ) alleviates the L-DOPA-induced dyskinesias in rats model of Parkinson’s disease [2]. Piribedil hydrochloride (oral gavage, 4-5 mg/kg, daily for 2 weeks) increases locomotor activity and reversal of motor deficits in adult common marmosets [3]. Piribedil hydrochloride (oral gavage, 150 mg/kg, daily for 21 days) inhibits MLL-r tumor growth and decreases the expression of MLL1 target genes in MV4;11 tumor xenografts [4]. Animal Model: Rat model of Parkinson’s disease [2] Dosage: 5, 15, 40 mg/kg Administration: Intraperitoneal injection, administered 5 min before administration of L-DOPA. Result: Reduced turning behaviour and AD (axial dystonia), OD (orolingual dyskinesia) and FD (forelimb dyskinesia) at 5 and 40 mg/kg. Increased LD (locomotive dyskinesias) at the 40 mg/kg. Animal Model: Adult common marmosets [3] Dosage: 4-5 mg/kg Administration: Oral gavage, daily for 2 weeks Result: Increased vigilance and alertness and reversed the downregulation of preprotachykinin mRNA induced by MPTP in rostral and caudal striatum.
