DG5128

DG5128 is a preferential α2-adrenoceptor antagonist. DG5128 exhibits 7.4 times higher affinity (pKi=6.28) toward α2-adrenoceptor than α1-adrenoceptor.

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

Research Areas >> Metabolic Disease

pKi :6.28 (α2-adrenoceptor)[1]

DG5128 (DG-5128) at concentrations up to 10 μM inhibits [3H]clonidine binding more effectively than it doed [3H]prazosin binding in rat cerebral cortex membranes. The mode of inhibition was homogeneous and consistent with the law of simple mass action[1]. The EC50 values for stimulation of insulin release from rat islets and the MIN6 β-cell line induced by DG5128 (Midaglizole) are 200 nM and 24 μM, respectively. The IC50 values for KATP current inhibition induced by DG5128 (Midaglizole) are 3.8 μM and 4.4 uM for Kir6.2 and Kir6.2/SUR1 , respectively[2].

DG5128 (3 and 30 mg/kg, i.v.) increases blood pressure in pithed rats[3].

Rats[3] Male Wistar rats (290-450 g) are anesthetized with pentobarbital sodium (35 mg/kg, i.p.) and artificially ventilated with room air. Diastolic blood pressure before the administration of the DG5128 (Midaglizole) is about 35 mmHg. DG5128 at doses of 3 and 30 mg/kg produces an increase in blood pressure by 27 and 64 mmHg, respectively, at approximately 1 min after the administration.

[1]. Yamanaka K, et al. The selectivity of DG-5128 as an alpha 2-adrenoceptor antagonist. Eur J Pharmacol. 1984 Nov 27;106(3):625-8.

[2]. Proks P, et al. Inhibition of recombinant K(ATP) channels by the antidiabetic agents midaglizole, LY397364 and LY389382. Eur J Pharmacol. 2002 Sep 27;452(1):11-9.

[3]. Hirohashi M, et al. Intrinsic pressor activity of midaglizole, an alpha-2 adrenoceptor antagonist, in pithed rats. Jpn J Pharmacol. 1990 Aug;53(4):519-20.

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