Bronchodilating and cardiovascular effects of intraduodenally and orally administered clenbuterol in dogs

Abstract

The bronchodilating and cardiovascular effects of intraduodenally and orally administered 4-amino-α[tert-butylamino)methyl]3,5-dichlorobenzylalcohol hydrochloride (clenbuterol, NAB 365) in anesthetized and conscious dogs were investigated and compared with those of salbutamol isoprenaline (isoproterenol) and (4-amino-3,5-dichloro-phenyl) glycolic acid (M-7), a metabolite of clenbuterol. In pentobarbitalized dogs, clenbuterol, 3-100 μg/kg i.d., inhibited the increase in air way resistance induced by histamine in a dose-related manner; clenbuterol was approximately 2 and 100 times more potent than salbutamol and isoprenaline, respectively. The plasma level of clenbuterol increased within 15 min and reached the maximum level within 60 to 990 min, which lasted for over 4 h after administration. The inhibitory effect was abolished by pretreatment with propranolol. M-7 showed no significant effect. In anesthetized dogs, clenbuterol and salbutamol, 10 and 100 μb/kg i.d., decreased arterial blood pressure and increased heart rate and maximum rate of rise of left ventricular pressure. Isoprenaline, 10 and 100 μg/kg i.d., caused no marked changes in these parameters. In conscious dogs, clenbuterol, 10 and 100 μg/kg p.o., and salbutamol, 100 μg/kg p.o., increased heart rate; the maximum responses were observed 1 to 2 h after administration and lasted for over 3 h. No marked effects were observed after salbutamol, 10 μg/kg p.o., isoprenaline, 10 and 100 μg/kg p.o., and M-7, 100 μg/kg p.o. The results indicate that clenbuterol, when administered intraduodenally and orally, is easily absorbed from the digestive tract and shows a potent inhibitory effect on histamine-induced bronchoconstriction with vasodilating and cardiac stimulating effects, and may manifest these activities through β-adrenoceptor stimulation.