THE INFLUENCE OF ANESTHESIA ON THE EVALUATION OF ANTITUSSIVE EFFECT

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Studies on the antitussive agents have been advanced with the development of bioassay for them. At the present time, a large number of non-narcotic synthetic antitussives are employed in the management of cough instead of narcotic antitussives.
The evaluation method for antitussive activity was first reported by Ernst in 1938 (1), that is, coughing was induced by pinching the trachea of a cat which had previously been made to sero-fibrinous pleurisy by means of intrapleural injection of Lugol solution. Two years later, Eichler and Smiatek (2) reported that coughing could be induced in the guinea pig by an inhalation of aerosolized sulfuric acid. However, these two methods have not been accepted widely for the evaluation of antitussive agents because of uncertainty of cough production. In 1952, Kasée devised two methods (3, 4): 1) electrical stimulation of the superior laryngeal nerve and 2) mechanical stimulation on the tracheal mucosa in the unanesthetized dog. At the same time, Domenjoz (5) reported a method, in which coughs were able to be induced by electric stimulation of the superior laryngeal nerve in the anesthetized cat. Kase as well as Domenjoz insisted that their own methods were suitable for the antitussive evaluation and the results obtained from the animal experiments were in good accordance with clinical effects. Since then, about thirty methods have been presented one after another for the evaluation of antitussive activity. However, they are classified in three groups after all: 1) mechanical stumulation method (3, 4, 6-13), 2) chemical one (2, 6, 8, 10-12, 14-20), and 3) electrical one (3, 5, 21-26).
Anesthesia is used in most of the methods described above. In general, anesthesia has been used as one of routine procedures in animal experiments, but cough reflex is affected by it to a great extent. If anesthesia is an inevitable procedure in the evaluation of antitussives, the influence of anesthesia on antitussive activity should be studied in detail. As far as we know, there has been no report on such study until the present. In the present paper, the influence of anesthesia on antitussive effect was studied in detail and a few remarks necessary for making use of anesthesia in the evaluation of antitussive agents were described.