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

The bronchodilating and cardiovascular effects of intraduodenally and orally administered 4-amino-alpha-[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-dichlorophenyl) glycolic acid (M-7), a metabolite of clenbuterol. In pentobarbitalized dogs, clenbuterol, 3-100 micrograms/kg i.d., inhibited the increase in airway 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 90 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 microgram/kg i.d., decreased arterial blood pressure and increased heart rate and maximum rate of rise of left ventricular pressure. Isoprenaline, 10 and 100 micrograms/kg i.d., caused no marked changes in these parameters. In conscious dogs, clenbuterol, 10 and 100 micrograms/kg p.o., and salbutamol, 100 micrograms/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 micrograms/kg p.o., isoprenaline, 10 and 100 micrograms/kg p.o., and M-7, 100 micrograms/kg p.o.(ABSTRACT TRUNCATED AT 250 WORDS)