Studies on Tetrahydroisoquinolines (Thi) (I) Bronchodilator Activity and Structure-Activity Relationship

Iwasawa, Yoshio; Kiyomoto, Akio

doi:10.1254/jjp.17.143

Cited by 99 publications

(56 citation statements)

References 5 publications

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“…Iwasawa et al (1) demonstrated that III possesses a strong bronchodilating action, which is about ten times in vitro and five times in vivo greater than that of Iso. It is interesting to note that in spite of the common susceptibility to the inhibition by pronethalol of the effects of III and Iso on the heart and trachea, the action of III on the cardiovascular system is weaker than that of Iso, wheras III has a stronger bronchodilating property than Iso.…”

Section: Discussionmentioning

confidence: 99%

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Studies on Tetrahydroisoquinolines (Thi) (Ii) Pharmacological Action on Cardiovascular System

1967

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Section: Discussionmentioning

confidence: 99%

“…Its bronchodilating activities in vitro and in vivo were about 10 times and 5 times stronger respectively than those of isoproterenol (1).…”

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Studies on Tetrahydroisoquinolines (Thi) (Ii) Pharmacological Action on Cardiovascular System

1967

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“…In 1967, Lands et al (1,2) proposed a classification of /3-adrenoceptors into two subtypes, (mediating the cardiac stimulation) and 82 (mediating the bronchial and vascular relaxation). Since then, many bronchodilators such as trimetoquinol (3,4), salbutamol (5), procaterol (6) and formoterol …”

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Tracheal Relaxing Effects and β2-Selectivity of TA-2005, a Newly Developed Bronchodilating Agent, in Isolated Guinea Pig Tissues

Kikkawa¹,

Naito²,

Ikezawa³

1991

Japanese Journal of Pharmacology

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ABSTRACT-Tracheal relaxing effects and /32-selectivity of TA-2005 were investi gated by functional experiments and radioligand binding assay in guinea pigs in com parison with those of other ,Q-agonists, isoproterenol, procaterol, formoterol and sal butamol. The relaxing activity of TA-2005 on histamine-induced contraction in the isolated trachea was most potent among the five agonists, and it was blocked by a 82 selective antagonist (ICI 118,551) but not by a /3,-selective antagonist (bisoprolol). The potency of the relaxing effect was in the order of TA-2005 (pD-, = 9.79) > for moterol > procaterol > isoproterenol > salbutamol. The positive chronotropic effect of TA-2005 was similar to that of isoproterenol; and it was more potent than those of formoterol, procaterol and salbutamol in the isolated atria. The selectivity for tracheal muscle to atria of these agonists were in the order of procaterol > formoterol > TA 2005 > salbutamol >> isoproterenol. A radioligand binding experiment using guinea pig lung and cardiac ventricle as ,82 and 81-adrenoceptor sources, respectively, has also demonstrated that TA-2005 possesses extremely high affinity (IC50 = 1.04 nM) and selectivity (38-fold) to X32-adrenoceptors. By addition of GTP, the competition curve of [1251 ]iodocyanopindolol shifted rightward, indicating the agonist property. These results confirmed that TA-2005 is a highly 82-selective agonist that exerts a po tent tracheal relaxing effect.

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“…EPI, norepinephrine (NOR) and trimetoquinol (TMQ) were used as sympathomimetics. TMQ is known to possess more potent (l-stimulating activity than isoproterenol in the tracheal muscle of guinea-pigs (4,5), and the drugs also showed only a fl-action in the skeletal muscles of rats and rabbits (2, 6), while isoproterenol had a weak a-action besides (l-action (6).…”

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Contractile Response to Sympathomimetic Amines in Isolated Rat Muscles After Chronic Denervation

Yamada

Harigaya

1974

Japanese Journal of Pharmacology

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It was demonstrated by Bowman et al (1) that an intravenous injection of epinephrine (EPI) caused an increase or a decrease in the tone of the chronically denervated cat mus cles and the effects were mediated by the (l-receptor. In our previous study in vivo (2), denervated rat muscles responded to EPI by a contracture mainly through the a-receptor, while rabbit muscles responded by a fall in the resting tension through both a and fl-re ceptors. The reason for the discrepancy is not clear, though it may in part be due to spe cies difference. In the present paper, effects of EPI and other adrenergic amines were fur ther studied in vitro using chronically denervated rat muscles.The sciatic nerve of male rats (Sprague-Dawly, 4-5 weeks of age) was sectioned under pentobarbital-Na anesthesia. The extensor digitorum longus muscle and the soleus mus cle were isolated 10-21 days after the operation and were suspended in a 10 ml bath of mammalian Ringer's solution according to Isaacson et al (3), which was aerated with a mixture of 95 %02 and 5 % CO2 and kept at 37-1-1°C (pH 7.5). In order to examine twitch response, field stimulation was applied to the muscle by platinum electrodes with the rec tangular pulses of suprarnaximal voltage and 5 cosec duration at 0.1 Hz frequency. The initial tension of the muscles was maintained within the range of 0. 1-0.3 g. Semi-isometric responses of twitch and resting tension were recorded on an ink-writing oscillograph through a strain gauge. Drugs were added to the bath in 0.1 ml volume to make the final required concentrations. EPI, norepinephrine (NOR) and trimetoquinol (TMQ) were used as sympathomimetics. TMQ is known to possess more potent (l-stimulating activity than isoproterenol in the tracheal muscle of guinea-pigs (4, 5), and the drugs also showed only a fl-action in the skeletal muscles of rats and rabbits (2, 6), while isoproterenol had a weak a-action besides (l-action (6).EPI in a concentration of 10-' g/ml caused an increase in the resting tension (con tracture) of the chronically dencrvated extensor digitorum longus muscle, as shown in Figs. I and 2. Higher concentration (10-6 10-5 g/ml) of the drug produced more remark able contracture with a steeper slope of rising phase and a larger peak of the tension, while lower concentration (10-e g/ml) sometimes failed to elicit the effect. This contractural response was differentiated into two components, a fast phase and a slow phase, which were sometimes observed very clearly as shown in Fig. 1-C. NOR produced similar con tracture to that by EPI_ TMQ caused only a slow phase of the contracture, the onset of

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Studies on Tetrahydroisoquinolines (Thi) (I) Bronchodilator Activity and Structure-Activity Relationship

Cited by 99 publications

References 5 publications

Studies on Tetrahydroisoquinolines (Thi) (Ii) Pharmacological Action on Cardiovascular System

Studies on Tetrahydroisoquinolines (Thi) (Ii) Pharmacological Action on Cardiovascular System

Tracheal Relaxing Effects and β2-Selectivity of TA-2005, a Newly Developed Bronchodilating Agent, in Isolated Guinea Pig Tissues

Contractile Response to Sympathomimetic Amines in Isolated Rat Muscles After Chronic Denervation

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