Imaging analysis of antiulcer action and the active constituent of Atractylodis rhizoma

Examination of the sizes of gastric mucosal injury has been conducted by visual means. However, the human visual-eye examination may sometimes involve personal biases and errors. In order to reduce these errors, automated analytical apparatuses have been developed. The equipment is generally expensive. In the present study, a low-cost imaging analytical method to examine the antiulcer action of drugs is reported. By using our imaging analytical method, an antiulcer effect of herbal medicine was examined on hydrochloric acid-ethanol induced gastric mucosal injury. Acetone extract of Atractylodis Rhizoma was found to have antiulcer action. In addition, the examination of fractions of the acetone extract, obtained through column chromatography, indicated that atractylon, at 17.5 mg/kg, p.o. significantly inhibits gastric mucosal injury.     

Luminal acid in stress ulceration and the antiulcer action of verapamil in rat stomachs

The role of luminal acid and the influence of the antisecretory action of verapamil in stress ulcer prevention in rat stomachs have been studied. Intraperitoneally injected verapamil, 4 mg kg-1, inhibited gastric acid secretion and ulcer formation, however, a 2 mg kg-1 dose, which did not significantly influence acid output, also had an antiulcer effect. Intraperitoneal injection of bethanechol, 1.2 or 3.6 mg kg-1, increased gastric acid output, but did not influence stress-induced ulcer formation. Oral administration of HCl, 25 or 50 mu equiv, aggravated stress ulceration in a dose-dependent manner; this lesion-worsening effect was prevented by pretreatment with verapamil or bethanechol. The gastric luminal acid content in 2 h pylorus-ligated rats was similar in the groups given either bethanechol or HCl. These findings indicate that the antisecretory action of verapamil may not account for its antiulcer effect. It is suggested that endogenous and exogenous luminal acid may have different influences on stress ulcer formation.     

Role of adrenal gland hormones in the mechanism of antiulcer action of nimesulide and ranitidine

In the present study, we investigated whether the antiulcer effects of nimesulide (100 mg kg(-1) and ranitidine (150 mg kg(-1) were dependent on the adrenal cortex hormones. The antiulcer effects of nimesulide and ranitidine were examined in the indomethacin-induced gastric ulcer model in rats (first experiment). The mean ulcer areas in the control and ranitidine-treated groups were 11.1 +/- 3.18, 1.4 +/- 1.11 mm2, respectively. There was not any gastric damage in nimesulide-treated group. The mean ulcer area of control group (second experiment) administered metyrapone and indomethacin was 11.8 +/- 9.9, and it measured 2.0 +/- 1.41 mm2 in ranitidine-given group, while gastric damage was not observed in nimesulide-administered group. In adrenalectomized and indomethacin-treated rats (third experiment), the mean ulcer area was 17.9 +/- 11.5 mm2 in the nimesulide group, gastric ulcer was not seen in ranitidine group. In adrenalectomized rats (fourth experiment), the mean ulcer areas were 29 +/- 14.3, 23 +/- 11.2 and 1.3 +/- 2.4 mm2 in control group given indomethacin, only nimesulide or indomethacin + ranitidine, respectively. The obtained results indicated that adrenal cortex hormones played a role in antiulcer effect of nimesulide, but not ranitidine.     

A study on the aetiology of reserpine ulceration and the antiulcer action of solcoseryl in rat stomach

The aetiology of reserpine-induced gastric ulcer formation and the antiulcer effects of solcoseryl were studied in rats. Intraperitoneal injection of reserpine produced severe ulceration, as well as mast cell and histamine depletion, in the gastric glandular mucosa. Mepyramine and Cimetidine markedly antagonized the gastric lesions, but did not influence the reduced mast cell count; atropine pretreatment significantly inhibited both parameters. Intramuscular injection of solcoseryl lessened ulcer severity and prevented the decreased mast cell counts and histamine levels in reserpine-treated rats. However, the same dose of solcoseryl injected intraperitoneally was ineffective. Solcoseryl, irrespective of the route of administration, did not influence the gastric secretory activities of reserpine. It is concluded that resperine ulceration is both cholinergic- and histamine-mediated, and that the antiulcer effects of solcoseryl appear to be due to prevention of histamine depletion in the gastric mucosa.     

Healing-promoting action of teprenone, a new antiulcer agent on acetic acid ulcer in rats

Healing promoting action of teprenone on acetic acid ulcer in rats was assessed in comparison to that of cimetidine and proglumide by histological measurements. Teprenone (100 mg/kg X 2/day, p.o.) decreased the macroscopic ulcer index and the defective area in the ulcerated region by 32.0% and 33.3%, respectively. In addition, this drug increased the decreasing index of exposed ulcer floor and the mucosal regeneration index by 28.1% and 38.0%, respectively. However, the thickness of the ulcer base and the development index of collagen fibers were little affected by this drug. Cimetidine (100 mg/kg X 2/day, p.o.) showed a 27.2% decreasing action on the macroscopic ulcer index and a 31.3% increasing action on the thickness of the ulcer base, but failed to increase the mucosal regeneration index. Specimens from the cimetidine-treated rats were characterized by marked granulation proliferation beneath the ulcer floor. The upper layer of the granulation tissue was very rich in inflammatory cells. Proglumide (250 mg/kg X 2/day, p.o.) was scarcely effective on any parameters. These results indicate that teprenone remarkably promotes the regeneration of the defective mucosa during the ulcer healing process, and the effectiveness of cimetidine according to the macroscopic observation may be due to excessive formation of granulation tissue in the defective region.     

Mechanism of the action aminopyrine]

In acute experiments on unanesthetized cats with a single and paired stimulation the effect of aminopyrine (5-30 mg/kg, intravenously) on bioelectric reactions in the conduction system of afferent impulsation at the thalamo-cortical level was studied. Aminopyrine is shown to highten the amplitude of an evoked potential of the somato-sensory cortex and of the specific transmitting nucleus of the thalamus upon stimulation of the radial nerve and to significantly lengthen with paired stimulation the regeneration period of the neuronic systems excitability in the structures under review. Investigations into the states of the cortical neuronic systems proper showed aminopyrine capable of increasing the number of high-frequency oscillations and the amplitude of the interzonal response as well as to lengthen with paired stimulation the restoration period of the neuronic systems excitability.     

注射用潘托拉唑钠抗实验性急性胃溃疡作用研究

目的 研究注射用潘托拉唑钠对大鼠和小鼠急性胃溃疡动物模型的影响.方法 采用小鼠水浸应激性胃溃疡模型,大鼠幽门结扎胃溃疡模型,同时观察幽门结扎大鼠胃酸分泌情况.结果 静脉注射潘托拉唑钠5,10,20mg·kg~(-1),对小鼠水浸应激性胃溃疡具有减少溃疡发生的作用,4,8,16mg·kg~(-1)对幽门结扎大鼠的胃溃疡面积具有明显的缩小作用,两者均呈剂量依赖性.对胃酸的分泌具有较强的抑制作用,对胃蛋白酶活性也具有抑制作用.上述结果与同剂量的奥美拉唑比较作用相似.结论 注射用潘托拉唑钠对大鼠小鼠实验性急性胃溃疡具有明显的保护作用.     

Studies on the synthesis of antiulcer agents. VI. Synthesis and antiulcer activity of dihydrobenzofuranone derivatives

The derivatives (2) of 3-(2,3-dihydro-2,2-dimethyl-3-oxo-5-benzofuranyl) acrylic acid (2b) were synthesized. The compounds (3a-g) in which bromo, methoxy, nitro, amino or acetamido group was introduced on the benzene ring of the derivatives (2) and the compounds (3h-k) in which acryloyl moiety was introduced on the 6- or 7-position of the benzofuranone skeleton also synthesized. Furthermore, propionic acid derivatives (4a-c), acetic acid derivatives (4d-g), formic acid derivatives (4h-k) and oxyacetic acid derivatives (5) were prepared by converting the acryloyl moiety of the derivatives (2) into propionyl, acetyl, formyl and oxyacetyl groups. These compounds were tested for antiulcer activities. Among these compounds, 1-[3-(2,3-dihydro-2,2-dimethyl-3-oxo-5-benzofuranyl)acryloyl]piperidine (2d) and 4-[3-(2,3-dihydro-2,2-dimethyl-3-oxo-5-benzofuranyl)acryloyl] morpholine (2g) were found to have stronger antiulcer activities.     

Mechanism of the anti-anginal action of korinfar

The effect of corinfar on the blood plasma Ca2+ content and oxyhemoglobin dissociation curve was studied in 52 patients with ischemic heart disease. The drug was administered in a dose of 60 mg/day and to 5 patients in a dose of 90 mg/day for 2 weeks. A complete disappearance of angina attacks and ECG normalization were observed in 37 patients, a good effect was noted in 30 patients and no effect was seen in 13 patients. A significant decrease of Ca2+ content during treatment was noted in patients with effort angina of mild and moderate degrees. Parallelism between Ca2+ content decrease and the drug efficacy was revealed.     

Mechanism of the anti-alcohol action of fenazepam

Experiments were performed on 64 albino male rats selected according to their ethanol preference. A long-term administration of ethanol produced a number of specific changes in the activity of the enzymes involved in metabolism of ethanol, lipid peroxidation, enzymes of metabolism of xenobiotics. At the continuous ethanol administration, phenazepam was found to normalize the activity of ethanol-metabolizing enzymes, both in vivo and in vitro. Phenazepam also normalized reaction of lipid peroxidation both in vivo and in vitro. The drug was shown to be an inductor with respect to enzymes of xenobiotic metabolism.     

Mechanism of action of the analgesic flupirtine

To answer the questions of mode and site of action partly supplementary, partly new investigations with flupirtine (Katadolon) were carried out which are described below. The investigation for opiate receptor affinity of flupirtine in rat brain homogenate did not show any reduction in 3He-etorphine binding up to the highest concentration of flupirtine of 10(-5) mol/1. This result suggests that flupirtine either has a very low opiate receptor affinity or lacks it fully. Therefore the analgesic activity of flupirtine is not based on opiate mechanism. The intracerebroventricular and intrathecal administration of flupirtine and the other analgesics tested showed dose dependent analgesic activity in doses which, when applied systemically, did not cause any analgesia in rats. Thus these substances show cerebral or spinal analgesic activity. In relation to the effective doses (ED50 in micrograms/rat) flupirtine was of the same efficacy in both kinds of administration. Pethidine tested comparatively was found to be less potent by intrathecal than by intracerebroventricular application. On the other hand, morphine was weaker by intracerebroventricular than by intrathecal application. As in the experiments by oral administration, naloxone did not show any effect on the analgesic activity of flupirtine, neither by intracerebroventricular nor by intrathecal application. On the other hand, the analgesic effects of pethidine and morphine were completely suppressed by naloxone. These results demonstrate that the analgesic activity of flupirtine is not caused by the opiate mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanism of the cardiotoxic action of palytoxin

Palytoxin (PTX) is a non-12-O-tetradecanoylphorbol-13-acetate-type tumor promoter that has potent cardiotoxic properties. In embryonic chick ventricular cells, PTX increased [Ca2+]i (K0.5 = 5 nM) in a manner that was dependent on the presence of extracellular Ca2+. The action of PTX was not consequent to its depolarizing action, to the opening of voltage-dependent Ca2+ channels, to an intracellular Na+ load, or to intracellular acidification. Flow cytometric analysis of the [Ca2+]i distribution in PTX-treated cells showed that only the largest ventricular cells responded to the toxin. All ventricular cells responded to PTX by intracellar acidification. PTX also increased 22Na+ uptake by cardiac cells (K0.5 = 100 nM) via a pathway that was sensitive to 3,4-dichlorobenzamil (K0.5 = 8 microM), suggesting a possible involvement of the Na+/Ca2+ antiporter. We conclude that the action of PTX in chick cardiac cells is distinct from that in erythrocytes or in fibroblasts and that it likely involves several distinct mechanisms. A primary action of PTX could be to open a Ca2+ uptake pathway in the plasma membrane, which would then trigger 22Na+ uptake by the Na+/Ca2+ antiporter.     

Mechanism of action of the diazabicyclononanone-type kappa-agonists

The 2,4-di-2-pyridyl-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9-one 1,5-diester HZ2 was recently found to exhibit high affinity and selectivity to the kappa-opioid receptor (KOR) in combination with an unusually long duration of action. Docking of HZ2 to the putative binding site model of the KOR revealed HZ2 to be tightly sitting in the binding pocket. Strong interactions, especially salts bridges between the protonated nitrogens of HZ2 and the glutamic acids 209 and 297, nicely explain the high affinity of HZ2 to the KOR. A formation of a hemiaminal bond between the keto carbonyl group of HZ2 and a lysine residue (Lys200) may explain the long duration of action.     

Studies on the synthesis of antiulcer agents. IV. Synthesis and antiulcer activity of dihydrobenzofuranone derivatives

The derivatives of 3-[3-oxospiro[benzofuran-2(3H),1'-cyclopropan]-5-yl]acrylic acid were synthesized and tested for antiulcer activities. As a result, 1-[3-[3-oxospiro[benzofuran-2(3H),1'-cyclopropan]-5- yl]acryloyl]piperidine(3t) and 4-[3-[3-oxospiro[benzofuran-2(3H),1'-cyclopropan]-5- yl]acryloyl]morpholine(3u) exhibited potent antiulcer activities.     

Studies on the synthesis of antiulcer agents. V. Synthesis and antiulcer activity of dihydrobenzofuranone derivatives

In the preceding paper, we reported that 1-[3-[3-oxospiro[benzofuran-2(3H),1'-cyclopropan]-5- yl]acryloyl]piperidine(1a) and 4-[3-[3-oxospiro[benzofuran-2(3H),1'-cyclopropan]-5- yl]acryloyl]morpholine(1b) have potent antiulcer activities. In this paper, propionic acid derivatives (2,3) and oxyacetic acid derivatives (4, 5, 10) were prepared by converting the acryloyl moiety into propionyl and oxyacetyl groups, and tested for antiulcer activities. As a result, [3-oxospiro[benzofuran-2(3H),1'-cyclopropan]5-yloxy]-a cetamide(4j) exhibited significant antiulcer activities.