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)