Delving into the Latest Updates on TASK-2 Activators(LifeArc) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

K2P activators

Target

KCNK

Mechanism

KCNK agonists(Potassium two pore domain channel subfamily K agonists)

Therapeutic Areas

Nervous System Diseases

Active Indication

Migraine DisordersPain

Inactive Indication-

Originator Organization

Lifearc

Active Organization

Lifearc

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Wagers, Mikaela L. ; Ahmed, Sufia ; Moon, Madison ; Cooper, Robin L. ; Ashley, Clair ; West, Aaron K. ; Ison, Bethany J. ; Bolton, Kayli E. ; Phe, Panhavuth ; Bledsoe, Constance O. ; Taylor, Isabelle N. ; Henning, Jamie N. ; Alhamdani, Abraham W. ; Tanner, Hannah N. ; Stonecipher, Samuel B. ; Bidros, Patrick C. ; Turner, Logan T. ; Abul-Khoudoud, Maya O. ; Capili, Jerone G.

The resting membrane potential enables neurons to rapidly initiate and conduct electrical signals. K2p channels are key in maintaining this membrane potential and electrical excitability. They direct the resting membrane potential toward the K+ equilibrium potential. Doxapram is a known blocker for a subset of K2p channels that are pH sensitive. We assessed the effects of 0.1 and 5 mM doxapram on the neural activity within the propodite-dactylopodite (PD) proprioceptive sensory organ in the walking legs of blue crabs (Callinectes sapidus). Results indicate that 0.1 mM doxapram enhances excitation, while the higher concentration 5 mM may over-excite the neurons and promote a sustained absolute refractory period until the compound is removed. The effect of 5 mM doxapram mimics the effect of 40 mM K+ exposure. Verapamil, another known K2p channel blocker as well as an L-type Ca2+ channel blocker, reduces neural activity at both 0.1 and 5 mM. Verapamil may block stretch activated channels in sensory endings, in addition to reducing the amplitude of the compound action potential with whole nerve preparations. These findings are notable as they demonstrate that doxapram has acute effects on neurons of crustaceans, suggesting a targeted K2p channel. The actions of verapamil are complex due to the potential of affecting multiple ion channels in this preparation. Crustacean neurons can aid in understanding the mechanisms of action of various pharmacological agents as more information is gained.

100 Deals associated with TASK-2 Activators(LifeArc)

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