Tachykinin receptor antagonists and cough

Area of Science:

• Pharmacology
• Neuroscience
• Respiratory Medicine

Background:

• Tachykinins are neurotransmitters with diverse physiological roles.
• Tachykinin receptors (NK1, NK2, NK3) mediate various biological effects.
• Investigating tachykinin receptor involvement in cough is crucial for therapeutic development.

Purpose of the Study:

• To evaluate the efficacy of selective tachykinin receptor antagonists in modulating cough.
• To identify the specific tachykinin receptor subtypes involved in cough reflex pathways.
• To explore the potential peripheral and central sites of action for these antagonists.

Main Methods:

• Utilized selective tachykinin NK1, NK2, and NK3 receptor antagonists (e.g., SR 48968, MEN 10627, SR 142801).
• Assessed antagonist effects on cough induced by chemical (citric acid, capsaicin) and mechanical stimuli in animal models (guinea-pig, cat).
• Investigated antagonists with limited blood-brain barrier penetration to infer peripheral versus central mechanisms.

Main Results:

• Tachykinin NK2 receptor antagonists significantly inhibited cough induced by various stimuli in guinea-pigs and cats.
• An NK3 receptor antagonist showed inhibitory effects on citric acid-induced cough in guinea-pigs.
• NK1 receptor antagonist effects on cough remain inconclusive.
• Evidence suggests a predominantly peripheral site of action, though central effects cannot be ruled out.
• Tachykinin NK2 receptor stimulation appears to sensitize the cough reflex.

Conclusions:

• Selective tachykinin NK2 receptor antagonists are potent inhibitors of cough.
• Tachykinin NK2 receptor pathways are critically involved in cough reflex sensitization.
• Further research is needed to fully elucidate the role of NK1 and NK3 receptors in cough and the precise site of action of antagonists.