IP Library › Granted Patent US 12,268,683
Granted Patent B2
US 12,268,683 · App. 17/260,796 · Granted Apr 8, 2025

Compounds and methods for synergistic activation of M channels

Inventors: Geoffrey W. Abbott (Irvine, CA); Rian W. Manville (Irvine, CA)
Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
A61K31/4748A61K31/19A61K31/195A61K31/197A61K31/198A61K31/27A61K31/353A61K31/555
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Quick Facts
Patent No.
US 12,268,683
App. No.
17/260,796
Granted
Apr 8, 2025
Kind
B2
Abstract

A method of activating heteromeric KCNQ2/3, KCNQ3/5, or KCNQ4/5 voltage-gated potassium channels in a cell membrane is described, as are compositions for use with same, as well as methods of reducing neuronal excitability and of ameliorating symptoms of epilepsy, anxiety, neuropathic pain, hypertension, cardiovascular disease, a neurodegenerative disorder, alcohol withdrawal, cancer, inflammation, or ophthalmic disease in a subject. These KCNQ2/3 (or KCNQ3/5 or KCNQ4/5) channels are heteromers that comprise KCNQ2 (or KCNQ5) subunits and KCNQ3 (or KCNQ4) subunits. In one embodiment, the method comprises: (a) contacting the cell membrane with a first agent that binds a KCNQ2 (or KCNQ5) subunit; and (b) contacting the cell membrane with a second agent that binds a KCNQ3 (or KCNQ4) subunit.

Claims (9)

1. A composition comprising: 1-30 μM mallotoxin (MTX), 1-500 μM isovaleric acid (IVA), and about 1 μM retigabine (RTG).

2. The composition of claim 1 , wherein the IVA is present in an amount ranging from 1 to 100 μM.

3. The composition of claim 1 , wherein the MTX and IVA are each present in an amount ranging from 1 to 10 μM, and the RTG is present in an amount of about 1 μM.

4. A method of activating KCNQ2/3, KCNQ3/5, or KCNQ4/5 voltage-gated potassium channels in a cell membrane, said channels comprising KCNQ2 or KCNQ5 subunits, and further comprising KCNQ3 or KCNQ4 subunits, the method comprising contacting the cell membrane with a composition of claim 1 .

5. The method of claim 4 , wherein the cell is a neuron, myocyte, epithelial cell, or endothelial cell.

6. The method of claim 4 , wherein the cell membrane potential is −80 mV to +40 mV during the contacting of the cell membrane with the composition.

7. A method of reducing neuronal excitability in a subject, the method comprising administering to a subject in need thereof, the composition of claim 1 .

8. A method of ameliorating symptoms of epilepsy, in a subject, the method comprising administering to the subject a composition of claim 1 .

9. The method of claim 7 , wherein the first and second agents of the composition are each administered at a dose of 10-1000 mg/day.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 8, 2021
From: ABBOTT, GEOFFREY W.; MANVILLE, RIAN W.
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 055868/0451 →
Continuity (2)
Provisional Application 62700046 · Jul 18, 2018
Related Publication 20210267965A1 · Sep 2, 2021
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