A Ca2+ channel activator
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.
| Cell experiment [1]: | |
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Cell lines |
Guinea Pig and Calf Myocardial Cells |
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Preparation method |
Soluble to 100 mM in ethanol. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
280 nM, 5 minutes |
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Applications |
Bay k 8644 increased twitch tension in guinea pig atria without changing the time course of tension development. Bay k 8644 increased the action potential duration of calf ventricular muscle and Purkinje fibers. Bay k 8644 increased strontium currents and altered the time- and voltage-dependence of channel opening. |
| Animal experiment [2]: | |
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Animal models |
Male Sprague-Dawley rats |
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Dosage form |
Intraperitoneal administration, 0.5-4 mg/kg |
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Application |
Intraperitoneal administration of BAY K 8644 (0.5-4 mg/kg) induced an increase in blood pressure associated with bradycardia, increased tail-flick latency in response to radiant heat, decreased locomotion, induced muscle contraction, postural changes and also reduced reflex activity. BAY K 8644 (4 mg/kg, i.p.) significantly increased homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations in the cortex and striatum. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Thomas G, Chung M, Cohen C J. A dihydropyridine (Bay k 8644) that enhances calcium currents in guinea pig and calf myocardial cells. A new type of positive inotropic agent[J]. Circulation research, 1985, 56(1): 87-96. [2]. Bourson A, Moser P C, Gower A J, et al. Central and peripheral effects of the dihydropyridine calcium channel activator BAY K 8644 in the rat[J]. European journal of pharmacology, 1989, 160(3): 339-347. |
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