[Bronchodilating action of (--)-1-(3, 4, 5-trimethoxybenzyl)-7-hydroxy-1, 2, 3, 4-tetrahydroisoquinoloine HCl (l-MTI) (author's transl)]

Abstract

Bronchodilating action of l-MTI was investigated by intravenous administration to anesthetized animals and the results were compared to those seen with isoproterenol. Bronchoconstriction was induced by histamine or serotonin. Under pentobarbital anesthesia, the bronchodilating activity of l-MTI was approx. 1/20 that of isoproterenol in cats and dogs, but less than 1/100 that of isoproterenol in monkeys and guinea pigs. The results indicate that the bronchodilating activity of l-MTI is variable and species dependent. It was demonstrated, however, that in guinea pigs, l-MTI did not produce any bronchodilating activity, when the animals were anesthetized with urethane. The absence of the bronchodilating response in animals under this anesthesia was also seen in vagotomized, adrenalectomized and reserpinized, norepinephrine-infused guinea pigs. On the contrary, l-MTI exhibited the bronchodilating action in reserpinized, pithed or hexamethonium-treated guinea pigs anesthetized with urethane. On th other hand, isoproterenol produced a bronchodilating action in all preparations mentioned above. It was also evident that l-MTI suppressed the bronchodilating action of isoproterenol in pentobarbital anesthetized guinea pigs. In addition, l-MTI increased the heart rate of guinea pigs with a low beating rate, but decreased it when the control rate was high. These results suggest that at least in guinea pigs, l-MTI acts as a partial agonist and that the effect of l-MTI on the bronchial system depends on the sympathetic tone and/or sympathetic bronchodilator reflex, as proposed by McCULLOCH ET AL. (9).