An adenylyl cyclase inhibitor
IC50: 1.5 X 10-5 M for histamine-stimulated adenylate cyclase [1].
RMI 12330 A is N,-(cis-2-phenylcyclopentyl) azacyclotridecan-2-imine hydrochloride, which has been reported to inhibit choleratoxin-induced intestinal hypersecretion, presumably via an inhibition of mucosal adenylate cyclase.
In vitro: RMI 12330 A at the concentration of ranging from 10 uM to 5 mM the can effectively inhibit the adenylate cyclase activity of a rat liver plasma membrane preparation. RMI 12330 A does not apply its competition on the catalytic site of the enzyme to perform its inhibitory action. The inhibition activity of RMI 12330 A upon adenylate cyclase was due to an irreversible binding with the plasma membranes [2].
Ex vivo: In the isolated work-performing heart of the guinea-pig, RMI 12330A depressed all cardiac functions with the IC50 of 1.1 X 10-6 M, including contractile force, dP/dt, dF/dt, pressures developed, stroke work and work performance. The positive inotropic response to increasing heart rate (staircase) and left atrial pressure rose became negative. Ouabain, isoprenaline and histamine, no longer had positive inotropic effects. After its depression by RMI 12330A, the cardiac function can be completely restored by increasing the perfusate calcium concentration from 2.5 mm to 4.5 and 6.5 mm [1].
Clinical trial: So far, no clinical study has been conducted.
参考文献:
[1] Grupp G, Grupp IL, Johnson CL, Matlib MA, Rouslin W, Schwartz A, Wallick ET, Wang T, Wisler P.? Effects of RMI 12330A, a new inhibitor of adenylate cyclase on myocardial function and subcellular activity. Br J Pharmacol. 1980 Nov;70(3):429-42.
[2] Guellaen G, Mahu JL, Mavier P, Berthelot P, Hanoune J.? RMI 12330 A, an inhibitor of adenylate cyclase in rat liver. Biochim Biophys Acta. 1977 Oct 13;484(2):465-75.
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