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  • Title: [Profile of pharmacological actions of NAB 365 (clenbuterol), a novel broncholytic agent with selective activity on adrenergic beta2-receptors (author's transl)].
    Author: Engelhardt G.
    Journal: Arzneimittelforschung; 1976; 26(7a):1404-20. PubMed ID: 12768.
    Abstract:
    Effects of 4-amino-alpha-[(tert.-butylamino)methyl]-3,5-dichlorobenzyl alcohol hydrochloride (clenbuterol, NAB 365) on the adrenergic beta-receptors were investigated and compared with those of isoproterenol and salbutamol. The beta2-mimetic activity of clenbuterol on the smooth muscle of bronchi, uterus and vessels after i.v. injection corresponds to that of salbutamol in all laboratory animals. When given subcutaneously or as an aerosol clenbuterol is even somewhat more effective than isoproterenol. Clenbuterol differs from the known beta-mimetic drugs in its much longer duration of action. Therefore the integral of activity of single doses of clenbuterol, which are equally effective in the period of their maximal action, is remarkably greater than that of the other beta-mimetic substances. Clenbuterol differs from known beta-mimetic drugs used as bronchodilators in its efficacy after oral administration and in its mode of action on the heart. In the isolated auricle of the rabbit it has proved to be a weak partial agonist. In conscious rabbits, anesthetised guinea-pigs, dogs and cats the maximum of tachycardia obtainable by clenbuterol is lower than that of salbutamol. The higher degree of tachycardia in conscious dogs provoked by clenbuterol is a result of a reflex reaction to the vasodilation analogous to that of salbutamol. In higher doses clenbuterol shows beta1-blocking properties. Like other beta-blocking agents it owns qualities of a local-anesthetic and prolongs refractory period of the heart of guinea-pigs. In contrast to other beta-mimetic substances, clenbuterol causes only slight mobilization of heart muscle glycogen by doses higher than those which have broncholytic effects. The lipolytic and lactacidemia inducing activity of clenbuterol in rabbits corresponds to that of isoproterenol. The blood sugar is only slightly increased by clenbuterol as well as by other beta-mimetic agents. Degree and duration of action of clenbuterol and the other sympathomimetic amines on skeletal muscle of the cat shows parallelism with that of the broncholytic effect. In the rat clenbuterol inhibits the gastric secretion more than does isoproterenol. In contrast to other broncholytic substances, a very small dosage of clenbuterol is sufficient to protect rats against the liberation of histamine and serotonin caused by the anaphylactic reaction.
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