STUDIES ON TETRAHYDROISOQUINOLINES (THI) (VIII) PHARMACOLOGICAL PROPERTIES OF METABOLITES OF A NEW ADRENERGIC β-STIMULANT, TRIMETOQUINOL
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概要
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A new adrenergic β-stimulant, <I>l</I>-1-(3, 4, 5-trimethoxybenzyl)-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline HCI (trimetoquinol), exhibits strong bronchodilator effect as well as hypotensive, positive inotropic and chronotropic actions (1-7). Recently, the metabolic fate of this compound was studied in detail and it was found that part of trimetoquinol (TMQ) was O-methylated to form both 6 and 7-methoxytrimetoquinol (6 and 7-MeTMQ). Conjugated TMQ and conjugated MeTMQ with glucuronic acid were also found in the urine (8, 9).<BR> It has been reported that 3-methoxyisoproterenol, a metabolite of isoproterenol (Iso), acts like an adrenergic β-receptor blocker. Thus it inhibits the positive chronotropic and vasodepressor responses to Iso in the dog and cat (10, 11). The antagonistic relationship between epinephrine or norepinephrine and the corresponding methoxymetabolites (metanephrine or normetanephrine) was also observed on the isolated guinea-pig tracheal muscle (12), on the isolated perfused rat heart (13), or on the non-pregnant uterus of the cat (14). On the other hand, the nictitating membrane of the cat, the seminal vesicle of the guinea-pig and the heart rate of the dog in situ were sensitized to epinephrine by metanephrine (14).<BR> The present experiments were performed to investigate the possible adrenergic β-stimulating and β-blocking properties of the methoxymetabolites (6- and 7-MeTMQ) of TMQ, and the effects on the heart rate, blood pressure and histamine-induced bronchoconstriction were examined in the anesthetized cat. As to the conjugated metabolites with glucuronic acid, the experiments were not carried out in the present study, since their pharmacological activities were very weak, as examined on the isolated tracheal muscle of the guinea-pig, and also the acute toxicities of these metabolites were very low.
- 公益社団法人 日本薬理学会の論文
著者
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NAGAO TAKU
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd.
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KIYOMOTO Akio
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd.
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SATO Masanori
Biological and Chemical Reseach Labolatories, Tanabe Seiyaka Co., Ltd.
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MURATA Sakae
Biological Research Laboratory, Tanabe Seiyaku Co., Ltd.
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MURATA Sakae
Biological Research Laboratories, Tauabe Seiyaku Co., Ltd.
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NAKAJIMA Hiromichi
Biological and Chemical Reseach Labolatories, Tanabe Seiyaka Co., Ltd.
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NAGAO Taku
Biological Research Laboratories, Tauabe Seiyaku Co., Ltd.
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KIYOMOTO Akio
Biological and Chemical Reseach Labolatories, Tanabe Seiyaka Co., Ltd.
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