Nihon yakurigaku zasshi. Folia pharmacologica Japonica
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Nippon Yakurigaku Zasshi · Jun 1992
[Effects of KW-6055, a novel benzylpyridine derivative, on central cholinergic systems].
We examined the effect of KW-6055 [alpha-(p-butyrylamino-o-nitrobenzyl) pyridine], which has anti-amnesic activity, on the central cholinergic systems of rat frontal cortex using in vivo brain microdialysis. 1) KW-6055 (40, 160 mg/kg, p.o.) increased the extracellular level of ACh in normal rats (257 +/- 23, 202 +/- 24%). The stimulating effect of KW-6055 on ACh release was abolished by tetrodotoxin treatment, supporting that the released ACh was due to neuronal firing. Reserpine pretreatment decreased the effect of KW-6055, indicating that KW-6055 acted on cholinergic neurons through catecholaminergic neurons. 2) In basal forebrain-lesioned rats, KW-6055 (40 mg/kg, p.o.) significantly increased the extracellular level of ACh (251 +/- 22%) for more than 2 hr, which was longer than in normal rats. In conclusion, these results suggest that the stimulating activity on ACh release may be involved in the mechanism of the anti-amnesic effects of KW-6055.
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Nippon Yakurigaku Zasshi · May 1987
[Anti-inflammatory, analgesic and anti-pyretic activities of a new anti-inflammatory compound, 2-[4-(3-methyl-2-butenyl)phenyl] propionic acid (TA), in experimental animals].
Anti-inflammatory, analgesic and anti-pyretic activities of orally administered TA were investigated in experimental animals. Against acetic acid-induced vascular permeability in mice, carrageenin-induced hind paw edema in rats and ultra-violet ray-induced erythema in guinea pigs, TA produced a dose related inhibition at doses of 40-160 mg/kg, 10-40 mg/kg and 10-40 mg/kg, respectively. TA produced no inhibition against histamine-induced vascular permeability even at a dose of 200 mg/kg in rats. ⋯ These results suggest that anti-inflammatory, analgesic and anti-pyretic activities of TA are generally a little weaker than those of ibuprofen, and the mode of action of TA is similar to that of a typical acidic non-steroidal anti-inflammatory drug such as ibuprofen, indomethacin or phenylbutazone. The ulcerogenic activity of TA was about 2 and 4 times weaker than that of ibuprofen in rats and mice, respectively. TA showed a protective effect against gastric necrosis induced by HCl.(ABSTRACT TRUNCATED AT 250 WORDS)
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Nippon Yakurigaku Zasshi · Dec 1985
Comparative Study[The modes of anti-inflammatory and analgesic actions of 2-[4-(3-methyl-2-butenyl) phenyl] propionic acid (TA-60) and 2-[4-(2,2-dichlorovinyl) phenyl] propionic acid (TA-668) and effect of TA-60 on the gastrointestinal tract].
TA-668 and TA-60, potent anti-inflammatory compounds, showed no inhibition against the dextran-, the serotonin- and the carrageenin + prostaglandin E2 (PGE2)-induced hind paw edemas in rats and neither did typical acidic non-steroidal anti-inflammatory drugs (ANSAIDs) such as indomethacin. On the other hand, salicylic acid, mepirizole and tiaramide X HCl inhibited the hind paw edema induced by carrageenin + PGE2 in rats. TA-668 and TA-60 as well as other ANSAIDs inhibited the arachidonic acid (AA)-induced erythema, but did not inhibit the PGE2-induced erythema. ⋯ TA-60 showed a protective effect against gastric necrosis induced by necrotizing agents such as HCl, NaOH or NaOH + EtOH. TA-60 showed about a 4 times less potent activity than ibuprofen in delay of occurring time of castor oil-induced diarrhea in rats. These results suggest that the slight ulcerating effect of TA-60 on the gastrointestinal tract might be attributed to its gastric protective effect and slight decreasing effect on the gastrointestinal level of PGE2.
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Nippon Yakurigaku Zasshi · May 1984
[Anti-inflammatory activity of a non-steroidal anti-inflammatory agent, oxaprozin, in experimental models].
Anti-inflammatory activity and mode of action of oxaprozin, a new non-steroidal anti-inflammatory agent, were investigated in experimental animal models and in vitro tests. Anti-inflammatory potency of oxaprozin was almost equal to that of aspirin in acetic acid vascular permeability, carrageenin hind paw edema, cotton pellet granuloma and adjuvant arthritis tests in rats. On the other hand, in mice, oxaprozin was more potent than aspirin, ibuprofen and phenylbutazone, and it was as potent as sulindac and fenbufen in acetic acid vascular permeability and carrageenin hind paw edema tests. ⋯ However, in mice, oxaprozin had a low metabolic rate, and the effect of oxaprozin was as potent as sulindac and fenbufen. The elimination half-life of oxaprozin is extended, 49 to 69 hr, in humans. It was suggested from these findings that oxaprozin is a potent and long acting anti-inflammatory drug in clinical use.
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Nippon Yakurigaku Zasshi · Feb 1983
[Effects of lorcainide, a new antiarrhythmic agent, on experimental cardiac arrhythmias].
Antiarrhythmic actions of lorcainide were compared with those of disopyramide on different types of arrhythmias in animal models. It was shown in dogs that lorcainide and disopyramide were approximately equipotent against the arrhythmias following coronary occlusion. ⋯ In the arrhythmias induced by the application of acetylcholine on the right auricle of guinea pigs, the disappearance of P-waves and the disturbance of R-R intervals were inhibited by disopyramide, but lorcainide had no influence on these events; both prevented the atrial fibrillation induced by acetylcholine application. Both drugs by themselves induced ventricular arrhythmias in guinea pigs.