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Pharmacological characterization of B-HT 933 (2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo-[5,4-d]-azepindihydrochloride) as a hypotensive agent of the “Clonidine-type”

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Summary

The hypotensive action of a new compound, B-HT 933 (2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo-[5,4-d]-azepin) was characterized to be of the “clonidine-type” by the use of 6 pharmacological test procedures. (1) Intravenous injection of the substance elicited a typical cardiovascular reaction pattern of initial hypertension, followed by hypotension with bradycardia and decreased cardiac output. (2) A direct α-adrenoceptor stimulation at peripheral vascular sites was demonstrated by a hypertensive action in spinal rats. (3) A central nervous site of action was shown as 30 μg/kg injected intracisternally (i.ci.) lowered blood pressure and heart rate in cats, but the same dose i.v. was practically ineffective. (4) The decrease in sympathetic activity was revealed by a decrease in preganglionic splanchnic nerve discharges in cats. (5) The drug facilitated the vagally-mediated baroreceptor reflex as shown by the increase in reflex bradycardia following i.v. angiotensin injection in dogs. (6) The involvement of central nervous α-adrenoceptors was suggested because the α-adrenoceptor blocking drug piperoxan antagonized the facilitation of the baroreceptor reflex induced by B-HT 933. Furthermore, the drug facilitated the flexor reflex in rats with spinal section at midthoracic level. These results were unexpected as the chemical structure of B-HT 933 differs considerably from hitherto known substances of the “clonidine-type”.

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  1. Pharmakologische Abteilung, Ernst Boehringer-Institut für Arzneimittelforschung, Dr. Boehringer-Gasse 5-11, A-1121, Wien, Austria

    W. Kobinger & L. Pichler

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  1. W. Kobinger
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  2. L. Pichler
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Kobinger, W., Pichler, L. Pharmacological characterization of B-HT 933 (2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo-[5,4-d]-azepindihydrochloride) as a hypotensive agent of the “Clonidine-type”. Naunyn-Schmiedeberg's Arch. Pharmacol. 300, 39–46 (1977). https://doi.org/10.1007/BF00505078

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  • DOI: https://doi.org/10.1007/BF00505078

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