1 The anti-tussive effects, of the local anaesthetic,
lidocaine and
carcainium chloride (
RSD931) have been investigated in guinea-pigs and rabbits. 2 Pre-treatment of guinea-pigs with
aerosols of
lidocaine or
RSD931 at 0.1, 1.0 and 10 mg ml(-1) reduced the number of
citric acid-induced
coughs by 9.3, 32.6 and 40.9% (P>0.05) for
lidocaine and by 25.3% (P>0.05), 40.4% (P>0.05) and 97.6% (P<0.01) for
RSD931, respectively and increased the latency to onset of
cough at 10.0 mg ml(-1) only. In addition,
RSD931 at 10 mg ml(-1) reduced
citric acid-evoked
cough responses in rabbits (with prior exposure to
ozone at 3 p.p.m. for 1 h) from 22.1+/-5.1 to 2.7+/-0.9
coughs (P<0.01). 3 Acute pre-treatment of guinea-pigs with
aerosols of
lidocaine or
RSD931 at 10.0 and 30.0 mg ml(-1) reduced the number of
capsaicin-evoked
coughs by 42.2 and 10.3% (P>0.05) (
lidocaine) and by 25% (P>0.05) and 76.9% (P<0.01) (
RSD931), respectively.
Lidocaine had little effect on the latency of
cough onset at either 10.0 or 30.0 mg ml(-1), however, RSD at 30.0 mg ml(-1) significantly (P<0.05) prolonged the latency of
cough onset. 4
RSD931 (10.0 mg ml(-1)) significantly (P<0.05-<0.01) reduced the spontaneous and
histamine-evoked discharges in Adelta-fibres originating from airway, rapidly adapting stretch receptors (RARs) without affecting
histamine-evoked bronchoconstriction.
Lidocaine at 10.0 mg ml(-1) also significantly (P<0.05) inhibited the spontaneous and
histamine-induced discharges of RARs without affecting
histamine-evoked bronchoconstriction. 5
Aerosols of
RSD931 (10.0 mg ml(-1)) caused a transient, but significant (P<0.05), activation of pulmonary C-fibre endings 2.5 min after administration started.
RSD931 had no significant (P>0.05) effects on discharges in bronchial C-fibres originating from bronchial C-fibre endings,
capsaicin-evoked discharges of either pulmonary or bronchial C-fibre endings or on
capsaicin-evoked bronchoconstriction. In contrast,
lidocaine (10.0 mg ml(-1)) significantly (P<0.05) inhibited spontaneous and
capsaicin-induced discharges in both pulmonary and bronchial C-fibres respectively.
Lidocaine also significantly (P<0.05) reduced
capsaicin-evoked bronchoconstriction. 6 These studies suggest that the anti-tussive actions of
RSD931 are mediated via inhibition of discharges in Adelta-fibres originating from airway RARs. The mechanism of action of
RSD931 is distinct from that of the local anaesthetic
lidocaine and
RSD931 may represent a novel class of anti-tussive agent.