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Biomedical subjects

H Tanizawa

Publications and source records attributed to H Tanizawa.

At least 55 records · Page 3Linked to original sources
PubMed1979

[Pharmacological studies of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101). (3). General pharmacological actions (author's transl)].

General pharmacological actions of M73101, a new non-steroidal analgesic anti-inflammatory drug were investigated in mice, rats, guinea pigs, rabbits, cats and dogs. Intravenous administration of M73101 produced a slight transient fall in blood pressure, an increase in heart rate and a respiratory stimulation, but no remarkable change in the electrocardiogram. The contraction induced by epinephrine in the isolated ear vessels of rabbits relaxed by M73101. In the isolated trachea of guinea pigs, M73101 relaxed the contraction induced by histamine. Furthermore, M73101 inhibited the bronchoconstriction by histamine but not by bradykinin in guinea pigs. These properties of M73101 on the tracheal smooth muscle were similar to those seen with aminopyrine but different from those seen with aspirin which inhibited only the contraction by bradykinin in vivo, suggesting that M73101 is a compound with properties similar to basic non-steroidal anti-inflammatory drugs. M73101 inhibited the intestinal propulsion in mice and also the gastrointestinal movement in rats and dogs. Moreover, M73101 showed a spasmolytic activity on the isolated ileum of guinea pigs, but such was not due to any specific antagonistic action on the chemical mediators. On the other hand, M73101 had no effect on the isolated uterus and vas deferens of rats. M73101, unlike aminopyrine and phenylbutazone, slightly increased urine volume and electrolytes excretion in rats, indicating that this compound probably does not produced edema. M73101 showed no significant pharmacological activities on the blood sugar level, blood coagulation, platelet aggregation, methemoglobin formation and local irritation.

Animals↗
PubMed1979

A new nonsteroidal analgesic-antiinflammatory agent. Synthesis and activity of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone and related compounds.

In order to examine analgesic and antinflammatory activities, various 2-alkyl- or 2-alkenyl-4-alkoxy-5-(substituted amino)-3(2H)-pyridazinones were prepared. Among the compounds prepared, 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (8) was evaluated to be the most attractive compound as an analgesic-antiinflammatory agent. Compound 8 was shown to be more potent in analgesic and antiinflammatory activities and less potent in toxicity than aminopyrine and phenylbutazone. Some pyridazinone derivatives in which possible active sites of 8 are eliminated and altered were prepared, and their activities were evaluated by means of analogous assays. On the basis of available data, the structure-activity relationship in a series of 4-alkoxy-2-substituted-5-(substituted amino)-3(2H)-pyridazinones was also discussed.

Acetates↗
PubMed1979

[Pharmacological studies of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101). (2). Anti-inflammatory activity (author's transl)].

The anti-inflammatory activity and the mode of action of M73101, a new non-steroid analgesic anti-inflammatory agent, were investigated in experimental animals and compared with those of reference drugs. M73101 inhibited the increase in vascular permeability induced by acetic acid and its activity was more potent than that of phenylbutazone. M73101 showed a marked inhibitory effect against rat paw edema induced by various phlogistic agents (carrageenin, dextran, histamine, serotonin and bradykinin) and the activities were equal to or more potent than those of aminopyrine, mepirizole and tiaramide HCl. M73101 also inhibited the edema induced by mustard, scalding and anti-rat rabbit serum in rats. In addition, the anti-edematous effect of M73101 on carrageenin-induced rat paw edema was not influenced by spinalectomy or adrenalectomy, indicating that the anti-inflammatory action of M73101 was not mediated by the central nervous system and the adrenals. Local and oral administration of M73101 inhibited significantly the leucocyte migration into the fluid of CMC pouch in rats and the activity was more potent than phenylbutazone, suggesting that the anti-inflammatory effect of M73101 was due to the direct action at the inflamed site. On the other hand, M73101 did not show any marked activities on the experimental chronic inflammatory models. From these results, it is suggested that M73101 may be useful for clinical application as a basic analgesic, anti-inflammatory drug with remarkable anti-inflammatory activity in acute and subacute cases. The mechanism of the anti-inflammatory action of M73101 probably involves inhibition of an increase in vascular permeability and leucocyte migration.

Adrenalectomy↗
PubMed1979

[Pharmacological studies of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101). (4). Enzyme induction (author's transl)].

The effect of M7310U, a new non-steroidal analgesic anti-inflammatory agent, on liver microsomal drug-metabolizing enzymes was investigated. Rats were treated orally with M73101 (100, 200, 500 mg/kg), henylbutazone (PZ, 200 mg/kg), aminopyrine (AM, 100 mg/kg) or phenobarbital sodium (PB, 100 mg/kg) once daily for 2 weeks and then were observed for 2 weeks during which treatment was not given. On treatment with M73101, PZ, AM and PB, the liver enlarged but was restored to normal 1 week after the last administration. The rate of increase in the case of M73101 was lower than that seen with the reference compounds. M73101 markedly increased the content of microsomal protein, cytochrome P-450 or b5 and NADPH cytochrome C reductase, aniline hydroxylase and AM demethylase activity, but these increments returned to the normal level 1 week after the last administration. The serum concentration of M73101 after repeated administration (200 mg/kg, p.o.) for 1 week was lower than that after a single administration. Furthermore, M73101 increased Vmax for both aniline hydroxylase and AM demethylase, whereas it increased Km only for aniline hydroxylase. M73101 did not enhance the lipid peroxidation. Our observations suggest that the enlargement of rat liver seen with M73101 was due to the induction of drug-metabolizing enzymes and that this agent can probably be classified as a phenobarbital-type inducer.

Aminopyrine N-Demethylase↗
PubMed1978

[Studies on the influsion speed and acute toxicity of amino acid solutions in rats (author's transl)].

Relationships between the infusion speed and lethal dose of several amino acid solutions of various concentrations were studied in male Sprague Dawley rats. When the amino acid solutions were continuously infused at various speeds, a functional relationship between the dose producing a cardiac arrest (DCA) and infusion speed was established. The DCA/infusion speed was characterized by two ranges with an increasing DCA as increase or decrease of infusion speed and by its intermediate range of a flat minimum with a practically constant DCA regardless of varying the infusion speed. A practically constant LD50 was obtained in the infusion of each amino acid solution within the infusion speed in the intermediate range. The LD50 of each amino acid solution was dependent on the crystalloid osmotic pressure.

Amino Acids↗
PubMed1978

[Pharmacological studies of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone (M73101). (1). Analgesic activity (author's transl)].

The analgesic activity and the mode of action of M73101, a new analgesic anti-inflammatory agent, were investigated in mice and rats and compared to those of reference drugs. M73101 showed a marked analgesic activity against noxious stimuli induced by pressure (Haffner method and Randall-Selitto method), thermal (hot plate method), electric and chemical (acetic acid-stretching method and bradykinin-induced responses) stimulation, in a manner similar to those of basic anti-inflammatory drugs (BAD) such as aminopyrine, mepirizole, tiaramide HCl, and benzydamine HCl. The activities of M73101 were equal to and/or more potent than those of BAD, and more potent than those of acidic anti-inflammatory drugs. In addition, the analgesic activity of M73101 was not decreased by the pretreatment with levallorphan and showed no cross-tolerance to morphine in mice, indicating that the analgesic properties of M73101 differ from those of morphine. On the other hand, the analgesic activity of M73101 as well as BAD was decreased by repeated oral administration in mice, and the potency was weaker than mepirizole. Furthermore, the muscle relaxant effect of M73101 obtained by inclined screen test in mice was the weakest among the BAD, suggesting that analgesic activity of M73101 is not related to the muscle relaxant property. These results indicate that M73101 may be useful for clinical application as an anti-inflammatory drug possessing remarkable analgesic activity.

Administration, Oral↗
PubMed1976

[Experimental studies on anthelmintics (XXVI). Biochemical and pharmacological studies of 4-iodothymol on Ascaris lumbricoides suum].

We have shown previously that 4-iodothymol (IT) produces a contraction in Ascaris muscle, probably due to the myogenic action. In this paper, the effects of IT on the carbohydrate metabolism in Ascaris muscle have been investigated in comparison with those of hexylresorcinol (Hex), santonin (S) and piperazine (Pip). (1) Hex (200 approximately 400 mug/ml) showed a strong nonspecific inhibition on the formation of succinate from fumarate in muscle homogenate, the phosphofructokinase (PFK) activity in cytoplasm, and the electron transfer activity in mitochondria. (2) S(100 approximately 400 mug/ml) and Pip (100 approximately 400 mug/ml) were inneffective on these activities. (3) IT inhibited the formation of succinate from glucose and fumarate in muscle homogenate (100 approximately 400 mug/ml), the PFK activity in cytoplasm (400 mug/ml), and the mitochondrial succinate oxidase system (25 approximately 400 mug/ml). These results suggest that IT elicits the wormcidal action by inhibiting the energy metabolism of Ascaris muscle mitochondria.

Animals↗