A-1048400 is a novel, orally active, state-dependent neuronal calcium channel blocker that produces dose-dependent antinociception without altering hemodynamic function in rats

2012 ◽  
Vol 83 (3) ◽  
pp. 406-418 ◽  
Author(s):  
Victoria E. Scott ◽  
Timothy A. Vortherms ◽  
Wende Niforatos ◽  
Andrew M. Swensen ◽  
Torben Neelands ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Active State ◽  
State Dependent ◽  
Hemodynamic Function ◽  
Orally Active ◽  
Dose Dependent ◽  
Neuronal Calcium Channel

Depolarization-stimulated cholecystokinin secretion is mediated by L-type calcium channels in STC-1 cells

1996 ◽  
Vol 270 (2) ◽  
pp. G287-G290 ◽  
Author(s):  
A. W. Mangel ◽  
L. Scott ◽  
R. A. Liddle
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Single Channel ◽  
Bay K 8644 ◽  
Ic50 Value ◽  
Single Channel Currents ◽  
Dose Dependent ◽  
Cck Release

To examine the role of calcium channels in depolarization-activated cholecystokinin (CCK) release, studies were performed in an intestinal CCK-secreting cell line, STC-1. Blockade of potassium channels with barium chloride (5 mM) increased the release of CCK by 374.6 +/- 46.6% of control levels. Barium-induced secretion was inhibited by the L-type calcium-channel blocker, nicardipine. Nicardipine (10(-9)-10(-5) M) produced a dose-dependent inhibition in barium-stimulated secretion with a half-maximal inhibition (IC50) value of 0.1 microM. A second L-type calcium-channel blocker, diltiazem (10(-9)-10(-4) M), also inhibited barium-induced CCK secretion with an IC50 value of 5.1 microM. By contrast, the T-type calcium-channel blocker, nickel chloride (10(-7)-10(-8) M), failed to significantly inhibit barium-induced CCK secretion. To further evaluate a role for L-type calcium channels in the secretion of CCK, the effects of the L-type calcium channel opener, BAY K 8644, were examined. BAY K 8644 (10(-8)-10(-4) M) produced a dose-dependent stimulation in CCK release with a mean effective concentration value of 0.2 microM. Recordings of single-channel currents from inside-out membrane patches showed activation of calcium channels by BAY K 8644 (1 microM), with a primary channel conductance of 26.0 +/- 1.2 pS. It is concluded that inhibition of potassium channel activity depolarizes the plasma membrane, thereby activating L-type, but not T-type, calcium channels. The corresponding influx of calcium serves to trigger secretion of CCK.

State-dependent properties of a new T-type calcium channel blocker enhance CaV3.2 selectivity and support analgesic effects

Pain ◽  
2013 ◽  
Vol 154 (2) ◽  
pp. 283-293 ◽  
Author(s):  
Amaury Francois ◽  
Nicolas Kerckhove ◽  
Mathieu Meleine ◽  
Abdelkrim Alloui ◽  
Christian Barrere ◽  
...  
Keyword(s):  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Analgesic Effects ◽  
State Dependent

ZC88, a novel N-type calcium channel blocker from 4-amino-piperidine derivatives state-dependent inhibits Cav2.2 calcium channels

2015 ◽  
Vol 1605 ◽  
pp. 12-21 ◽  
Author(s):  
Shuzhuo Zhang ◽  
Lujia Yang ◽  
Kang Zhang ◽  
Xiaoyan Liu ◽  
Weiwei Dai ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
State Dependent
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