The localization of the central
cough mechanism was studied by electrically stimulating the lower brainstem in cats lightly anesthetized with
pentobarbital sodium or in unanesthetized midcollicular decerebrate preparations.
Cough responses were recorded with the aid of a microphone. The
cough responsive region was concentrated in an area dorsomedial to the trigeminal tract and nucleus. The sites of action of
antitussive agents (
dextromethorphan,
codeine,
clonazepam,
diazepam and
caramiphen) were studied on the centrally induced
cough responses. Each of these drugs was administered intravenously to determine the dorsal levels for
cough suppression. In other series, the threshold dose via the intravertebral route was determined first. Because the agent necessary to prevent
cough via this route was so small in amount, recovery usually occurred in 20 to 90 minutes. Then the same agent was given intravenously in an attempt to obtain an effective dose which was close to the minimum dose for blocking the
cough. The mean effective doses of these agents to abolish the
cough via the vertebral artery were only about 1/20 of those required via
intravenous injection. The findings suggest that these agents act centrally to suppress the
cough responses.
Clonazepam was found to be the most potent
antitussive among these agents, the mean effective dose being about 1/35 of that of
codeine. The
antitussive potency of
benzodiazepines is not well correlated with their muscle relaxant activity. For instance,
clonazepam and
diazepam have the same potency in depressing polysynaptic spinal reflexes, whereas the former is 6 times more potent than
diazepam as an
antitussive. This finding indicates that
clonazepam has a high specificity as an
antitussive.