Akira Takanaka

Showa Pharmaceutical University

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Kannosuke Fujimori

Pharmaceuticals and Medical Devices Agency

Yoshihito Omori

National Institute of Health Sciences

Kazuhide Inoue

Kyushu University

Ken Nakazawa

Saitama Medical University

Ryuichi Kato

Muroran Institute of Technology

S Nakaura

National Institute of Health Sciences

Momoko Sunouchi

National Institute of Health Sciences

Toru Kawanishi

Tokyo Institute of Technology

Kunio Kawashima

National Institute of Infectious Diseases

Satoru Tanaka

Japan Agency for Marine-Earth Science and Technology

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National Institute of Health Sciences

115

The University of Tokyo

National Institute of Health Sciences

Kyushu University

Osaka University

Tohoku University

Kyoto University

Keio University

Hokkaido University

Nihon University

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METABOLISM OF DRUGS IN OLD RATS (I) ACTIVITIES OF NADPH-LINKED ELECTRON TRANSPORT AND DRUG-METABOLIZING ENZYME SYSTEMS IN LIVER MICROSOMES OF OLD RATS

The Japanese Journal of Pharmacology (1968)

Ryuichi Kato Akira Takanaka

Many lipid soluble compounds are metabolized by liver microsomes in the presence of oxygen and NADPH (1, 2). It has been considered that NADPH oxidizing system of liver microsomes is the responsible component for the oxidation and reduction of drugs (1-3). The metabolisms (oxidation and reduction) of drugs by liver microsomes are altered by diet, age and sex as well as by some unphysiological conditions (4-8). The alterations in the metabolisms of drugs are often accompanied with similar alterations in the activities of NADPH-linked electron transport system of liver microsomes (3, 4, 8-10). In a previous paper we reported a marked age differences in the oxidation of drugs, such as, hexobarbital, pentobarbital, meprobamate and carisoprodol by liver microsomes in the female rats (6). The activities of drug oxidations are almost zero at the birth and then rapidly increased upto 30 days, but the activities again decreased slightly with maturing in female rats. On the other hand, the activities in male rats are still increased with maturing and then slightly decreased (11). The purpose of present studies is the determination of the activities of drug-oxidizing and -reducing systems in old rats (about 600 days old) in comparison with young adult rats (about 100 days old). Moreover, it is of interest to investigate whether or not decreased activities in drug-oxidation and -reduction in old rats is related to those of NADPH-linked electron transport systems of liver microsomes. Many activities of drug oxidation show a clear sex difference and the activities are dependent on male sex hormone (6, 12). In the present experiments, therefore, the male and female rats were used for the study of the effect of male sex hormone in old rats.

10.1254/jjp.18.381

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Citations (91)

DRUG AFFECTING THE GASTRIC EMPTYING RATE AND DRUG ABSORPTION

The Japanese Journal of Pharmacology (1972)

Ryuichi Kato Akira Takanaka Kin-ichi ONODA Yoshihito Omori

In a previous paper (1) we reported that administration of sucrose markedly decreased the rate of gastric emptying and of intestinal absorption of aminopyrine in intact rats. These results indicated that the rate of gastric emptying markedly affected the rate of drug absorption and the onset and intensity of drug actions.

Absorption rate

10.1254/jjp.22.434

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Citations (7)

The Circumstances of Present Guidelines for Nonclinical Pharmacokinetic Studies from Establishment to Revision.

Drug Metabolism and Pharmacokinetics (1997)

Akira Takanaka

10.2133/dmpk.12.213

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Cytotoxic effects of methylnitrosourea on developing brain

Neurochemical Research (1983)

Kannosuke Fujimori Momoko Sunouchi Kazuhide Inoue Masahiro Nakadate Akira Takanaka

10.1007/bf00963920

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Citations (3)

Antagonism by reactive blue 2 but not by brilliant blue G of extracellular ATP‐evoked responses in PC12 phaeochromocytoma cells

British Journal of Pharmacology (1991)

Kazuhide Inoue Ken Nakazawa Mica Ohara‐Imaizumi Tomoko Obama Kannosuke Fujimori

The effects of reactive blue 2 and brilliant blue G, which have been shown to block extracellular ATP‐evoked responses, were investigated to discover whether these compounds act as P 2 ‐purinoceptor antagonists in PC12 phaeochromocytoma cells. Reactive blue 2 (10 to 100 μ m ) suppressed the ATP‐stimulated dopamine secretion from PC12 cells in a dose‐dependent manner. The concentration‐response curve for ATP was shifted to the right and the maximal response was decreased by reactive blue (30 and 100 μ m ). Brilliant blue G (up to 100 μ m ) did not significantly affect the secretion. Reactive blue 2 (10 to 100 μ m ) suppressed the ATP‐activated inward current recorded from the voltage‐clamped cells in a concentration‐dependent manner. Brilliant blue G (up to 100 μ m ) did not affect the current. The results suggest that reactive blue 2 but not brilliant blue G is a P 2 ‐purinoceptor antagonist in PC12 cells. The purinoceptors in these cells may be the same type as those involved in ATP‐evoked smooth muscle relaxation, judging from the antagonism by reactive blue 2.

10.1111/j.1476-5381.1991.tb12265.x

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Citations (39)

Behavioral pharmacological studies of various chemicals in MAO inhibitor-treated animals(Report 2). Effects of p-chlorophenylalanine on rat behavior by L-DOPA combination, and study of a new analytical method of conditioned avoidance response

The Japanese Journal of Pharmacology (1982)

Shigeyuki Nagao Takahiko Endo Kin-ichi ONODA Akira Takanaka Yoshihito Omori

10.1016/s0021-5198(19)54203-2

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Extracellular ATP-evoked norepinephrine release coupled with receptor-operated Ca permeable channels in PC12 cells

The Japanese Journal of Pharmacology (1990)

Kazuhide Inoue Ken Nakazawa Kannosuke Fujimori Tomoko Obama Isao Saito

10.1016/s0021-5198(19)55126-5

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Citations (2)

[Studies on the teratogenic potential of sodium dehydroacetate in rats].

PubMed (1988)

Shinji Tanaka K Kawashima S Nakaura Susanthy Djajalaksana Akira Takanaka

Source

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Citations (2)

[Effect of methyl hesperidin on the prenatal development of rats].

PubMed (1986)

K Kawashima S Nakaura M Usami Motoko Yamaguchi Satomi Tanaka

Prenatal development

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INHIBITION OF DRUG-METABOLIZING ENZYMES OF LIVER MICROSOMES BY HYDRAZINE DERIVATIVES IN RELATION TO THEIR LIPID SOLUBILITY

The Japanese Journal of Pharmacology (1969)

RYUIGHI KATO Akira Takanaka Hatsue Shoji

The activity of drug-metabolizing enzymes of liver microsomes is inhibited by various compounds and the administration of these compounds markedly alters the pharmacological activities of other drugs (1-3). Iproniazid is a well-known inhibitor of monoamine oxidase and it was the first compound of hydrazine derivatives as the inhibitor of drug metabolizing enzymes (4). Moreover, the other monoamine oxidase inhibitors, such as JB 516 (phenylisopropylhydrazine) and W 1544 (phenethylhydrazine) inhibited the metabolism of hexobarbital and meprobamate (5-7). La Roche and Brodie (6) showed that the activity of these compounds as the inhibitor of hexobarbital metabolism is not related to their ability to inhibit monoamine oxidase. On the other hand, it has been established that the compounds of low lipid solubility are not metabolized by liver microsomes (8). It is, therefore, likely that the lipid solubility of hydrazine derivative may be an important factor for the inhibition of drug-metabolizing enzymes. In the present communication, we wish to report that isoniazid and many other hydrazine derivatives inhibit the oxidation of hexobarbital, pentobarbital, meprobamate and carisoprodol and the N-demethylation of aminopyrine both in vitro and in vivo in relation to their lipid solubility. These results are typical example to show that the lipid solubility of compounds is more important factors rather than their chemical configuration for the inhibition of drugmetabolizing enzymes of liver microsomes.

Hexobarbital

Iproniazid

Hydrazine (antidepressant)

Meprobamate

10.1254/jjp.19.315

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Citations (34)