Preliminary Assessment of Deptropine Dihydrogen Citrate in Chronic Airways Obstruction.

The synthesis and the chemical properties of the compound 3-(10,1 1-dihydro-5H-dibenzo[a,d]cyclohepten-5-yloxy)-tropane citratel and a number of its congeners have been described by van der Stelt, Harms, and Nauta (1961). Funcke, de Jonge, Tersteege, Mulder, Harms, and Nauta (1962) outlined the diverse pharmacological properties of deptropine and made particular note of its effect on broncho-constriction induced by histamine and serotonin asthma in guinea-pigs. These authors also observed that deptropine had an antihistaminic effect on the isolated guinea-pig intestine 80 times more potent than diphenhydramine hydrochloride and a cholinolytic action on the same preparation about three times more active than atropine sulphate. A similar compound, thiazinanium, with anticholinergic, antihistaminic, and antiserotonin properties, was found to be effective parenterally in reversible airways obstruction (Booy-Noord, Orie, ten Cate, Sloots, and Bolt, 1957; Van Geuns and Scherrer, 1955) although oral administration was surprisingly ineffective. Scherrer (1962) and Schmidt (1962) have described the clinical usefulness of the parenteral administration of deptropine in asthma and bronchitis. The former author compared the effect after three hours of the intramuscular administration of 2 or 3 mg. deptropine with 1% isoprenaline by aerosol and 0 25 g. aminophylline by intravenous injection, and found its action in increasing timed forced expiration to be three times as powerful as isoprenaline and six times as powerful as this dose of aminophylline. None of the published reports has objective proof that the drug is effective when administered orally. Scherrer (1962), on rather limited experience, doubted the efficacy of oral therapy. McNicol and Bruyns (1964) found active deptropine to have no significant advantage over placebo therapy in 22 patients suffering from chronic bronchitis, and it produced no sympto-