Effects of brotizolam and other diazepines on respiration.

The inhibitory influence on respiratory functions is clinically an important attribute of the diazepine drugs. This unwanted side effect is frequently observed with intravenous administration in anesthesiology. It is difficult to demonstrate when taken orally, however, of equal clinical relevance, e.g. in elderly people, in patients with obstructive airways diseases, and eventually also in healthy subjects, when diazepine are given for sleep improvement. In the present study, three diazepines, brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno [3,2-f]-1,2,4-triazolo[4,3-a]-1,4-diazepine, We 941, Lendormin), triazolam and flunitrazepam, which can be used as soporifics, are investigated comparatively in respect to their effect on respiration in anesthetized cats, using intravenous administration. For all three drugs, a marked toxic interaction was found with chloralose/urethane anesthesia, and noticeably less distinctive with pentobarbital anesthesia. This toxicity increased in quantity with the sequence brotizolam less than triazolam less than flunitrazepam. After repeated injections of equal or increasing doses, a pronounced tachyphylaxia was noted, whereby the tolerance against the toxic actions on respiration commenced already after the first injection. In case of flunitrazepam, however, was this tachyphylaxia clearly less prominent. Recently, similar results with diazepines were reported by several other authors. The various effects of diazepines on respiration and their conceivable mechanism of action are briefly discussed, and the relevance of the results in this context is evaluated.