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Biomedical subjects

H Fujimura

Publications and source records attributed to H Fujimura.

At least 217 records · Page 12Linked to original sources
PubMed1982

[Effect of tiemonium iodide on colonic motility in dogs].

Effects of tiemonium iodide (tiemonium, 20 micrograms/kg), mepenzolate bromide (mepenzolate, 20 micrograms/kg), butylscopolamine bromide (butylscopolamine, 50 micrograms/kg) and atropine sulfate (atropine, 10 micrograms/kg) on the colonic motility in dogs were evaluated using a balloon method. The frequency of the wave motion was analyzed by fast Fourier transform, and the power spectra were obtained. The value of the first term of the power spectrum is regarded as an indication of the colonic tonus. Inhibitory effects of tiemonium on both the normal proximal colonic motility and the accelerating motility induced by neostigmine metylsulfate (neostigmine, 50 micrograms/kg) were equal to those of butylscopolamine. In the case of distal colonic motility, tiemonium showed potent mepenzolate-like inhibition. When the drugs were injected into the veins after administration of PGF2 alpha (10 micrograms/kg), all of the drugs depressed the colonic constriction induced by PGF2 alpha. The colonic motility was not restored by the administration of tiemonium or mepenzolate before the injection of PGF2 alpha, but such an effect was not observed in the case of butylscopolamine and atropine. It is suggested that tiemonium shows an extensive inhibition on the colonic motility in the mode of mepenzolate-like action and by some additional mechanism.

Animals↗
PubMed1982

[Anti-inflammatory, analgesic and antipyretic activities of alpha-(p-thenoylphenyl)-propionic acid (TN-762) (author's transl)].

We reported in our previous paper that TN-762, a potent inhibitor of prostaglandin biosynthesis, has marked inhibitory activity on acute experimental inflammation. In this paper, the anti-inflammatory, analgesic, and antipyretic activities of TN-762 were assessed in animal models, and compared with those of indomethacin, ketoprofen and ibuprofen. TN-762 inhibited the sustained paw edema induced by mustard in rats during administration for 3 days, but after final administration, the inhibitory activity was decreased rapidly and was less then that of ketoprofen and indomethacin. TN-762 also inhibited the proliferation of granuloma induced by means of cotton pellet and granuloma pouch methods, and the adjuvant arthritis in rats. The inhibitory activity of the compound on inflammatory proliferation was more potent than that of ibuprofen, but slightly less than that of ketoprofen and less than about 1/10 times that of indomethacin. Indomethacin markedly inhibited the body weight gain at a high dose, while TN-762 did not affect it. Therefore, TN-762 was proven to have an inhibitory effect on subacute and chronic inflammation at low doses without toxic effects, but the compound appeared to have a less of an inhibitory effect on secondary or late stages of inflammation than on primary stage inflammation. TN-762 inhibited the acute paw edema induced by nystatin, and the inhibitory activity was the same as that of ketoprofen and indomethacin. The pathogenesis of nystatin edema has been considered to be due to lysosomal labilization. This result suggests that TN-762 has a potent membrane stabilizing action which is considered to be one of the necessary mechanisms in anti-inflammatory action. On the other hand, TN-762 showed the same potent analgesic effect as ketoprofen and indomethacin as observed by the acetic acid writhing and modified Haffner's methods in mice and by the Randall-Selitto's method in rats. However the antipyretic effect of TN-762 was significantly less than that of ketoprofen and indomethacin.

Analgesics↗
PubMed1981

[Pharmacological study of mequitazine (LM-209) (II). Anti-allergic action (author's transl)].

The anti-allergic effect of Mequitazine (LM-209) which was found to have an anti-histaminic activity was investigated in guinea-pigs. The inhibitory activities of LM-209 on the Schultz-Dale reaction and ileum contraction by some mediators released from the sensitized guinea-pig lung were the same as those of clemastine fumarate (CL) but with 5 times the potency. LM-209 and CL, but these activities were less potent than in the case of disodium cromoglycate. The various anaphylactic reactions mediated by IgG in guinea-pigs were inhibited by LM-209, CL and chlorpheniramine maleate (CPM). The homologous PCA mediated IgE in rats was also inhibited by LM-209, CL and CPM, but the duration of the action with LM-209 was markedly longer. In experimentally-induced asthma, the decrease of respiratory rate and volume was significantly inhibited by LM-209, but was not affected by CL. Thus, LM-209 seems to inhibit the allergic reaction mainly by an antagonistic action on allergic mediators.

Anaphylaxis↗
PubMed1981

Inhibition of adenylate cyclase by GTP and its modulation by opiate receptor in rat caudate nucleus.

Morphine inhibited the adenylate cyclase activity of the crude synaptosomal fraction of the rat caudate nucleus in the presence of BTP, GDP, Gpp(NH)p or ITP. The purine nucleotides themselves had an inhibitory action on the enzyme. Beta-endorphin and Met-enkephalin also inhibited the enzyme in the presence of GTP. The GTP-dependent in inhibitory action of morphine was blocked by naloxone. Various opiates and opioid peptides inhibited the enzyme by up to approximately 20 per cent in the presence of GTP. The relative potency was in higher order of levorphanol greater than beta-endorphin greater than Met-enkephalin greater than morphine greater than pentazocine. Levorphanol was about 50,000 times as potent as its biologically inactive enantiomer, dextrorphan. Morphine enhanced the inhibitory actions of GTP and GTPase-resistant Gpp(NH)p on the adenylate cyclase activity. These results suggest that GTP plays an important role in the regulation of adenylate cyclase activity in the rat caudate nucleus and that the occupation of opiate receptor by agonists inhibits the enzyme through an actual increase in the inhibitory action of GTP, rather than a suppression of the enzymatic degradation of GTP.

Adenylyl Cyclase Inhibitors↗
PubMed1981

[Pharmacological study of mequitazine (LM-209) (III). Action on the central nervous system (author's transl)].

The action of an anti-histaminic agent, Mequitazine (LM-209) on the central nervous system was investigated. We found that LM-209 did not affect the spontaneous and co-operative movement in mice, did not induce muscle relaxation, analgesic effects or anti-convulsant effect in micr or hypothermic effects in rats. The anti-oxotremorine effect of LM-209 in mice was about 10 times more potent than clemastine fumarate (CL) and the same as promethazine. The activity and duration of the action were also superior to diethazine and orphenadrine used as an anti-Parkinson drug. LM-209 prolonged by 50% the hypnotic time induced by hexobarbital at 50 mg/kg (p.o.) in mice, while CL prolonged 50 and 100% it at 25 and 50 mg/kg (p.o.) respectively. In the EEG of rabbits, LM-209 produced a resting pattern, inhibited the arousal responses and recruiting responses and the effect was the same as CL and less potent than promethazine. From these results, the activity of LM-209 on the central nervous system (except for the anti-oxotremorine effect) seems to be the same as or somewhat less potent than CL. Therefore LM-209 should be an effective and anti-histaminic agent for clinical application.

Analgesics↗
PubMed1981

[Pharmacological study of mequitazine (LM-209) (I). Antagonistic actions of chemical mediators (author's transl)].

Antagonistic activities of Mequitazine (LM-209) on chemical mediators and in particular histamine were investigated in guinea-pigs, mice and rats. The antagonistic activity of LM-209 for histamine in the isolated ileum and trachea of guinea-pigs was less potent than that for clemastine fumarate (CL) and chlorpheniramine maleate (CPM) while that for acetylcholine was more potent than CL and CPM. Moreover, the antagonistic activities of these three compounds on serotonin and bradykinin were almost equipotent in the excised ileum. Using a modified Konzett-Rössler method, the bronchodilating effect of LM-209 (p.o.) for histamine was same as CL, but that for acetylcholine was more potent than CL and CPM. The protective activity of LM-209 (p.o.) on acute death induced by histamine and metacholine in mice was the same as CL, but the duration of the anti-histaminic action was markedly longer than CL. LM-209 given orally inhibited markedly the increased vascular permeability by histamine in rats and the diarrhea by 5-HTP in mice, but did not affect on the histamine-induced ulcer in guinea-pigs. From these results, LM-209 appears to have potent and long acting antagonistic activity on various chemical mediators.

Acetylcholine↗
PubMed1981

[Effect of alpha-(p-thenoylphenyl)-propionic acid (TN-762) on acute inflammatory reactions and prostaglandin biosynthesis].

A series of compounds with the general structure of phenylpropionic acid was originally synthesized for anti-inflammatory screening. The title compound, TN-762, showed marked anti-inflammatory and analgesic activities and was less toxic. This compound was the same as suprofen which was reported by Janssen to have potent anti-inflammatory and anti-writhing activities. Effects of TN-762 on acute inflammatory reactions and prostaglandin biosynthesis were investigated in animal models and findings compared to those of ketoprofen and indomethacin. TN-762 showed a dose-dependent inhibition at low doses of 5-20 mg/kg, p.o. on an increased vascular permeability induced by histamine in rats and by acetic acid in mice and carrageenin-induced paw edema in rats. The anti-inflammatory activity of TN-762 was much the same as that of ketoprofen and indomethacin. The inhibitory effect of TN-762 on carrageenin-induced paw edema was not affected by successive administration for 14 days and/or by adrenalectomy. The compound was more active than the two reference compounds in inhibiting ultraviolet erythema in guinea pigs. TN-762 inhibited markedly the arachidonic acid potentiation of carrageenin-induced edema in rat paw, the sudden death following intraveneous administration of arachidonic acid to rabbits and the diarrhea produced by endotoxin in mice, all considered to be induced by biosynthetic prostaglandins. The activities of TN-762 were the same or were more potent than those of ketoprofen and indomethacin. On the contrary, the ulcerogenic activity of TN-762 on the gastrointestinal tract in rats was significantly less than that of ketoprofen and indomethacin. From the above results, TN-762 proved to be a potent inhibitor of acutely-induced inflammation and of prostaglandin biosynthesis, however, the ulcerogenic effects were comparatively diminished.

Animals↗
PubMed1981

[Interaction of phenothiazinic anti-inflammatory agent, protizinic acid, with the biopolymers: Inhibitory effects on functions of platelets (author's transl)].

Two types of phenothiazinic anti-inflammatory agents, protizinic acid (PZA) and metiazinic acid (MZA) were examined using 1) heat denaturation test, 2) heat-induced erythrocyte lysis, 3) several platelet functions, 4) model membrane systems containing the same phospholipids and cholesterol compositions as in platelets. PZA and MZA were inhibited with heat denaturation in a similar manner seen with BSA and heat-induced erythrocyte lysis, and effects were more potent than indomethacin (IM). PZA showed inhibitory effects similar to MZA on ADP or collagen-induced platelet aggregation. However, in arachidonic acid (AA)-induced rabbit platelet aggregation, PZA had a more potent effect, similar to effects seen with IM and more potent than those of MZA. PZA inhibited the lethal effect of AA in rabbits at concentrations lower then MZA. To determine the sites of action, we examined the effects on uptake and release reactions of 3H-serotonin. PZA and MZA did not affect the uptake reaction but did reduce the release of serotonin to a greater extent than seen with IM. The tested drugs had little effect on the platelet aggregation in vivo. To investigate the interaction of these drugs with lipid bilayers, we used liposomes as a model membrane, of which the lipids compositions were the same as that of platelets. The tested drugs showed inhibitions of the liposome aggregation with addition of 6 mM Ca2+, in a dose dependent manner and similar to findings in the drug-platelet system. In this experiment, PZA had a more potent interaction with lipid bilayers than did MZA. These results suggest that interactions of PZA with the platelet membrane may be the origin of the PZA-induced inhibition of the platelet aggregation, in addition to the effect on the biosynthesis of prostaglandins.

Animals↗
PubMed1981

[Topical anti-inflammatory activity of dexamethasone 17-valerate (author's transl)].

The anti-inflammatory activity of dexamethasone 17-valerate ointment (DV-17, 0.12%) was investigated by topical application in mice and rats, and the effects compared with those of dexamethasone (DX, 0.12%), betamethasone 17-valerate (BV-17, 0.12%), beclomethasone 17,21-dipropionate (BE, 0.025%) and hydrocortisone 17-butyrate (HC, 0.1%) which were prepared with the same ointment base. DV-17 inhibited markedly the superficial inflammation such as increased vascular permeability induced by intradermal injection of histamine or bradykinin in rats and edema induced by a drop of croton oil into the mouse ear. DV-17 also inhibited significantly rat paw edema induced by carrageenin, yeast, nystatin and mustard. The inhibitory activity of DV-17 on those acute inflammatory responses was similar to that of DX and BV-17. In the inhibitory activity on carrageenin induced paw edema, DV-17 was less potent than that of DX when given orally, however was similar to DX in topical application. DV-17 also inhibited granulation tissue proliferation by subcutaneous paper disk implantation and nontreated foot swelling in adjuvant arthritic rats, but the inhibitory activity of DV-17 on the inflammation of these distant areas was lower than that of DX. On the other hand, systemic effects such as decrease in weight of adrenal or thymus and body weight loss were most evident in the case of DX and lower with DV-17. DV-17 prolonged wound healing and inhibited the delayed-type hypersensitivity induced by picryl chloride. The activity was equivalent to that of DX and BV-17. From the above results, it may be considered that DV-17 possesses potent anti-inflammatory activity, whereas it has fewer side effects and is a useful glucocorticoid for external application.

Administration, Topical↗
PubMed1980

Antiinflammatory principles of Aconitum roots.

The methanol extracts of Aconitum roots have shown inhibition of increased vascular permeability induced by acetic acid and of hind paw edema produced by carrageenin in mice. The extract of A. carmichaeli has been fractionated, monitored by the capillary permeability test, to yield the aconitines as active principles. The aconitines have inhibited the increased vascular permeability induced by acetic acid in mice peritoneal cavity and that induced by histamine in rat intradermal sites, and the hind paw edema formation induced by carrageenin n rats and mice at low doses. The benzoylaconines have exhibited inhibitory effects of the aforementioned acute inflammations but at higher doses. The aconitines have reduced the granulation tissue formation of the chorio-allantoic membrane of the chick embryo. On the other hand, the Aconitum alkaloids have elicited no effects on the ultraviolet erythema formation in guinea pigs at lower doses than the lethal ones and failed to show positive responses on the vascular permeability in the granuloma pouch and on adjuvant arthritis in rats at the doses employed.

Acetates↗
PubMed1980

Interaction of indomethacin and aspirin or mepirizole in rats as shown by gastrointestinal ulcerogenic and anti-inflammatory activities.

The interaction of indomethacin and aspirin or mepirizole was studied in rats. Concomitant oral administration of aspirin and indomethacin had no significant influence on the gastro-ulcerogenicity of indomethacin alone, but caused significantly less intestinal damage than an identical dose of indomethacin alone. In proportion to the inhibitory activity of intestinal lesions, aspirin also showed the activity that antagonized significantly the shortening of small intestinal length, loss of body weight and delay of charcoal transport in the intestine induced by indomethacin alone. Aspirin tended to reduce also the anti-inflammatory and analgesic effects of indomethacin in combined administration. On the other hand, mepirizole significantly reduced both gastric and intestinal ulcerogenicities by indomethacin alone in concomitant oral administration and inhibited dose-dependently the incidence and severity of those lesions. The inhibitory activity of gastrointestinal lesions by mepirizole was in proportion to the activities that antagonized the shortening of the small intestine, loss of body weight and delay of charcoal transport by indomethacin. Moreover, in contrast to aspirin, mepirizole exerted more potent anti-inflammatory and analgesic effects in combined administration than in the single administration of indomethacin. Therefore, aspirin reduced both the intestinal side effect and the anti-inflammatory effect induced by indomethacin in combination, while the combination of mepirizole reduced the gastrointestinal side effects by indomethacin alone, but seemed to be additive in the anti-inflammatory effect.

Animals↗