Mechanism of Action
Tedisamil acts to restore normal electrical rhythm in the heart by prolonging the inactivation phase of the muscle. Both atrial and ventricular repolarization is lengthened by tedisamil by blocking multiple potassium channels including the transient outward (Ito), the adenosine triphosphate-dependent (IK-ATP), and the delayed rectifier potassium currents (IKr and IKs). Tedisamil action is dose dependent as currents are blocked longer and more effectively at higher concentrations. Tedisamil activity is greatest on Ito and acts by binding to the channel in its open configuration. This produces a blocked state and delays its inactivation. To restore normal function, tedisamil must unbind from the channel so that it can inactivate and eventually reopen. Similar mechanisms have been observed on the IKr and IKs currents. In both Ito and delayed rectifier channels, the tedisamil binding site appears to be internal as both binding and unbinding occur more effectively when tedisamil is applied inside the cell. Tedisamil also appears to provide specific, single channel blocking of IK-ATP at high concentrations. As the potassium channels are responsible for restoring the resting membrane potential during an action potential, lengthening their inactivation will stop the cycle of fibrillation by preventing muscle contraction until all ion channels are available to open. Regular use of tedisamil will prevent further fibrillation and restore normal electrical rhythm. Tedisamil’s antiarrythmic activity also appears to be supported by inhibiting sodium currents in cardiac muscle. However this is only observed at concentrations above 20μM, concentrations 20-fold higher than required for potassium channel blocks.
Read more about this topic: Tedisamil
Famous quotes containing the words mechanism of, mechanism and/or action:
“A mechanism of some kind stands between us and almost every act of our lives.”
—Sarah Patton Boyle, U.S. civil rights activist and author. The Desegregated Heart, part 3, ch. 2 (1962)
“When one of us dies of cancer, loses her mind, or commits suicide, we must not blame her for her inability to survive an ongoing political mechanism bent on the destruction of that human being. Sanity remains defined simply by the ability to cope with insane conditions.”
—Ana Castillo (b. 1953)
“Perhaps a modern society can remain stable only by eliminating adolescence, by giving its young, from the age of ten, the skills, responsibilities, and rewards of grownups, and opportunities for action in all spheres of life. Adolescence should be a time of useful action, while book learning and scholarship should be a preoccupation of adults.”
—Eric Hoffer (1902–1983)