Background:

EC50: Acting as a L-type Ca2+ channel activator with EC50 of 17.3 nM .

The advent of calcium channel activators makes it possible to increase the amount of ACh released from the nerve terminals during their activation. Being applied as a Ca2+ channel activator, BAY K 8644 generally exhibits positive inotropic and vasoconstrictor effects on heart and smooth muscle. [1]

In vitro: It was demonstrated that Bay K 8644 prolonged the mean Ca2+ channel opening time in heart myocytes and neurones of spinal ganglia. An experiment using rat heart ventricles demonstrated that Bay K 8644, at the final concentration of approximately 1 pM, had strong positive inotropic effect when added to the perfusion fluid. Moreover, the addition of Bay K 8644 to the chronic ethanol treatment significantly reduced the electrophysiological signs of withdrawal in the isolated hippocampal slices. [2, 3]

In vivo: Study in mice demonstrated that Bay K 8644 significantly ameliorated the ethanol withdrawal syndrome. When experimental animals were administered with an acute injection of Bay K 8644, the convulsive behavior of mice could be monitored to increase for 2 hours. In addition, BAY k 8644 was also reported to ameliorate hypotension in endotoxin-shocked rats. It could lead to a 37% decrease in heart rate of endotoxin-treated rats and 39% decrease in control rats in a dose-dependent manner. [3,4]

Clinical trial: So far, no clinical trial has been conducted.

参考文献:
[1]Greenberg DA, Cooper EC and Carpenter C.  Calcium channel 'agonist' BAY K 8644 inhibits calcium antagonist binding to brain and PC12 cell membranes. Brain Res. 1987. 305: 3658.
[2]Doledal V and Tucek S.  Failure of the calcium channel activator, Bay K 8644, to increase the release of acetylcholine from nerve terminals in brain and diaphragm. Br. J. Pharmac. 1987. 91: 475-9.
[3]Whittington MA, Butterworth AR, Dolin SJ, Patch TL and Little HJ.  The effects of chronic treatment with the dihydropyridine, Bay K 8644, on hyperexcitability due to ethanol withdrawal, in vivo and in vitro. Br. J. Pharmacol. 1992. 105: 285-92.
[4] Ives N, King JW, Chernow B and Roth BL.  BAY k 8644, a calcium channel agonist, reverses hypotension in endotoxin-shocked rats. Eur J Pharmacol. 1986. 130: 169-175.