Effect of the two tachykinin antagonists, SR 48968 and SR 140333, on cough induced by citric acid in the unanaesthetized guinea pig
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The combined effects of SR 48968 and salbutamol are studied to find out whether the antitussive effect of SR48968 is a consequence of the inhibition of bronchoconstriction, and whether tachykinin NK1 receptors are involved in cough.Abstract:
It is now well-established that sensory nerves stimulation in the airway induces bronchoconstriction and inflammation, but also protective reflexes, such as coughing. These effects are mediated through the release of tachykinins (substance P and neurokinin A) and we have recently shown that SR 48968, a tachykinin NK2-receptor antagonist, inhibited cough induced by citric acid. In this paper, we have studied the effects of SR 48968 administered by aerosol. We have also investigated the effects of SR 140333, a tachykinin NK1-receptor antagonist, and the combination of both SR 48968 and SR140333 to determine whether tachykinin NK1 receptors are involved in cough. Finally, we have studied the combined effects of SR 48968 and salbutamol to find out whether the antitussive effect of SR 48968 is a consequence of the inhibition of bronchoconstriction. Unanaesthetized guinea-pigs were placed in a transparent chamber and exposed to an aerosol of citric acid (0.4 M). The number of coughs was counted by visual inspection and by determination of sounds and pressure variations in the chamber. By the aerosol route, SR 48968 was an efficient antitussive and 16 times more potent than codeine. SR 140333 (0.1-1 mg.kg-1 i.p.) did not exert any antitussive effect but it potentiated the maximal effect induced by SR 48968. Finally, salbutamol, in a dose (0.3 mg.kg-1) which inhibits bronchoconstriction, but not cough induced by citric acid, did not modify the antitussive effect of SR 48968.(ABSTRACT TRUNCATED AT 250 WORDS)read more
Citations
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References
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A potent and selective non-peptide antagonist of the neurokinin A (NK2) receptor.
X. Emonds-Alt,P. Vilain,Pierre Yves Andre Goulaouic,Vincenzo Proietto,D. Van Broeck,Charles Advenier,Emmanuel Naline,Gervais Neliat,G. Le Fur,J.C. Brelière +9 more
TL;DR: SR 48968 is a potent and selective non-peptide antagonist of the neurokinin A (NK2) receptor and was a competitive antagonist of neurokinIn A-mediated contraction of different isolated smooth muscle preparations from various species including human.
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Afferent neural pathways in cough and reflex bronchoconstriction
TL;DR: Cough and bronchoconstriction are airway reflexes that protect the lung from inspired noxious agents and may be mediated by the same type of receptor, they seem to have separate afferent neural pathways.
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In vitro and in vivo biological activities of SR140333, a novel potent non-peptide tachykinin NK1 receptor antagonist
Xavier Emonds-Alt,Jean-Daniel Doutremepuich,Michel Heaulme,Gervais Neliat,Vincent Santucci,Régis Steinberg,P. Vilain,Daniel Bichon,Jean-Philippe Ducoux,Vincenzo Proietto,Didier Van Broeck,Philippe Soubrie,Gérard Le Fur,Jean-Claude Breliere +13 more
TL;DR: SR140333 potently, selectively and competitively inhibited substance P binding to NK1 receptors from various animal species, including humans, and exerted highly potent antagonism towardNK1 receptors in vitro and in vivo.
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Capsaicin inhalation in man and the effects of sodium cromoglycate
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TL;DR: Experiments using local anaesthesia applied to the buccal mucosa or larynx indicated that the cough was caused by the stimulation of capsaicin‐sensitive nerve terminals situated in the larynz, and cough response was not altered by the prior inhalation of sodium cromoglycate.
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Neurokinin A (NK2) receptor revisited with SR 48968, a potent non-peptide antagonist.
Charles Advenier,Rouissi N,Nguyen Qt,X. Emonds-Alt,J.C. Brelière,Neliat G,Emmanuel Naline,Regoli D +7 more
TL;DR: Because of its activity in human tissues, its potency and long duration of action, SR 48968 is a new promising pharmacologic and possibly therapeutic agent.