ICI-170777 

ICI-170777 is an orally active cardiotonic agent and type III Phosphodiesterase inhibitor, with an IC₅₀ of 2.5 μM against cyclic AMP phosphodiesterase type III from canine cardiac fractions. ICI-170777 inhibits Aldrin epoxidase and pentobarbital metabolism. It enhances β-adrenergic receptor-mediated positive inotropic effects without causing chronotropic effects, while also exerting balanced arteriolar/venular vasodilator, platelet aggregation inhibitor and smooth muscle relaxant activities. ICI-170777 restores cardiac function in an acute canine heart failure model, exhibits additive effects when combined with Ouabain (HY-B1457), and shows no significant activity against multiple receptor classes or non-cardiac systems. ICI-170777 can be used in research related to congestive heart failure^[1][2][3].

ICI-170777 potently inhibits fraction III phosphodiesterase isolated from dog ventricular tissue with an IC₅₀ of 2.5 μM^[3].
ICI-170777 (10^-7-10^-4 M) exerts a concentration-dependent β-adrenoceptor-independent positive inotropic effect on cat isolated papillary muscles^[3].
ICI-170777 (10^-7-10^-6 M) potently inhibits ADP (HY-W010918)- or collagen-induced in vitro platelet aggregation at concentrations of 10^-7 M to 10^-6 M^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

ICI-170777 (5-80 mg/kg; p.o.; daily; 14 days) dose-dependently inhibits rat hepatic microsomal aldrin epoxidase activity, with maximum inhibition (80% reduction from control) observed at 80 mg/kg daily for 14 days, without inducing changes to P450 isozyme profiles^[1].
ICI-170777 (1-12.5 mg/kg; p.o.; daily; 10 days) inhibits rat hepatic microsomal aldrin epoxidase activity at doses of 4 mg/kg and higher when administered daily for 10 days, with no inhibition observed at 1 or 2 mg/kg^[1].
ICI-170777 (1-80 mg/kg; p.o.; single dose) dose-dependently prolongs pentobarbitone-induced sleeping time in rats, with significant inhibition starting at 4 mg/kg, and the inhibitory effect persists for up to 24 hours post-dose^[1].
ICI-170777 (10 μg/kg-5000 μg/kg; i.v.; cumulative dosing) produces dose-dependent positive inotropic effects in chloralose-anaesthetized dogs, with atenolol pretreatment attenuating but not abolishing the response, requiring a mean dose of 1.82 mg/kg i.v. to evoke a 50% increase in left ventricular dP/dt_max^[2].
ICI-170777 (2-10 mg/kg; 5 mg/kg; p.o.; single dose; twice daily; 5 days) exerts a dose-dependent positive inotropic effect with minimal heart rate increase, balanced vasodilation, no tachyphylaxis, and a long duration of action in conscious dogs^[3].
ICI-170777 (50 μg/kg/min; i.v.; continuous infusion) reverses ethanol-induced acute left ventricular dysfunction in anaesthetised dogs by reducing cardiac filling pressure and increasing cardiac output^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

207.25

C₉H₉N₃OS

123297-52-9

O=C1SC(C)C(C2=CC=NC=C2)=NN1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. McKillop D, et al. Different inhibition and induction profiles of hepatic drug metabolism in rats and dogs by two structurally related pyridyl diazinone cardiotonic agents. Biochem Pharmacol. 1991 Feb 1;41(3):411-7.  [Content Brief]

  [2]. Collis MG, et al. The cardiovascular pharmacology of ICI 170777 ((6RS)-6-methyl-5-(pyrid-4-yl)-3H,6H-1,3,4- thiadiazin-2-one) a novel compound with positive inotropic and vasodilator effects. Br J Pharmacol. 1989 Jun;97(2):409-18.  [Content Brief]

  [3]. Collis M G. ICI 170777: a new compound with positive inotropic and vasodilator actions[J]. Cardiovascular Drug Reviews, 1991, 9(1): 18-29.