The prospect for potent sodium voltage-gated channel blockers to relieve an excessive cough

Title:

The prospect for potent sodium voltage-gated channel blockers to relieve an excessive cough

Creator:

Brozmanova, Mariana and Pavelkova, Nikoleta

Identifier:

https://cdk.lib.cas.cz/client/handle/uuid:07937c3f-303f-471c-9158-4a2a9c47efc3
uuid:07937c3f-303f-471c-9158-4a2a9c47efc3
doi:10.33549/physiolres.934395

Subject:

airway sensory nerves, A-fibers, C-fibers, cough, and voltagegated sodium channel blockers

Type:

model:article and TEXT

Format:

počítač and online zdroj

Description:

An excessive, irritable, productive or non-productive coughing associated with airway inflammation belongs to pathological cough. Increased activation of airway vagal nociceptors in pathological conditions results from dysregulation of the neural pathway that controls cough. A variety of mediators associated with airway inflammation overstimulate these vagal airway fibers including C-fibers leading to hypersensitivity and hyperreactivity. Because current antitussives have limited efficacy and unwanted side effects there is a continual demand for the development of a novel more effective antitussives for a new efficacious and safe cough treatment. Therefore, inhibiting the activity of these vagal C-fibers represents a rational approach to the development of effective antitussive drugs. This may be achieved by blocking inflammatory mediator receptors or by blocking the generator potential associated with the specific ion channels. Because voltage-gated sodium channels (NaVs) are absolutely required for action potentials initiation and conduction irrespective of the stimulus, NaVs become a promising neural target. There is evidence that NaV1.7, 1.8 and 1.9 subtypes are predominantly expressed in airway cough-triggering nerves. The advantage of blocking these NaVs is suppressing C-fiber irrespective to stimuli, but the disadvantage is that by suppressing the nerves is may also block beneficial sensations and neuronal reflex behavior. The concept is that new antitussive drugs would have the benefit of targeting peripheral airway nociceptors without inhibiting the protective cough reflex.

Language:

English

Rights:

http://creativecommons.org/publicdomain/mark/1.0/
policy:public

Coverage:

S7-S18

Source:

Physiological research | 2020 Volume:69 | Number:Supplement 1

Harvested from:

CDK

Metadata only:

false