In vitro characterization of the effects of MCI-154, anovel cardiotonic agent, on cardiac tissues.

Abstract

Abstract-In vitro cardiac effects of a cardiotonic drug, MCI-154, for which the main action mechanism was proposed to be the enhancement of Ca2+ sensitivity of cardiac contractile proteins, were investigated.MCI-154 (3X10-8-3X10-4 M) increased the developed tension in isolated ventricular muscles from cats, dogs, guinea pigs and rats and increased that of isolated left atrial muscles of guinea pigs and rats. However, species differences were observed in the responses to MCI 154. The positive inotropic potency of MCI-154 was stronger than those of amrinone and milrinone.In the isolated right atria from guinea pigs and rats, properties of the chronotropic effect of MCI-154 were different from those of amrinone and milrinone.The positive inotropic action of MCI-154 was not affected by phentolamine, propranolol, cimetidine and tetrodotoxin.

MCI‐154: A Second Generation Ca2+ Sensitizer That Does Not Impair Relaxation — A Novel Approach to the Treatment of Heart Failure

“…At concentrations of 10 -7 -10 -5 M, MCI-154 did not bind to a-, b 1 -, or b 2 -adrenergic receptors, angiotensin II receptors or Ca 2+ channels (Kawasumi and Kitada, unpublished data). Unlike digitalis, MCI-154 had no effect on the activity of Na + -K + -ATPase, isolated from rat brain (38).…”

“…At concentrations higher than 10 -6 M MCI-154 inhibits delayed rectifier K + current in guinea pig hearts (12,20) and at 10 -7 -10 -6 M it stimulates Ca 2+ uptake by sarcoplasmic reticulum in dog hearts (38). These findings might partly explain why MCI-154 has a negative chronotropic action in isolated guinea pig right atrial preparations without causing diastolic dysfunction (7).…”

“…CGP 48506 and EMD directly act on actin-myosin reaction. Modified with permission from Nielsen-Kudsk and Aidershvile(38).…”