The protective effect of a new antiallergic agent, KP-136 on mast cell activation: A comparison with disodium cromoglycate

Kuriyama, Kiyoshi; Hiyama, Yoshiyuki; Itō, Kiyoshi; Yoshinaka, Ichiro; Bito, Yukio

doi:10.1007/bf01965038

Cited by 10 publications

(2 citation statements)

References 17 publications

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“…However, sodium cromolyn is known to inhibit histamine release from human lung mast cells 32 . The inhibitory effects of disodium cromoglycate work at the first antigen-dependent and extracelluar Ca 2+ -independent stage of the mast cell activation processes in rats, increasing membrane permeability and causing an influx of extracellular calcium in the second stage prior to the degranulation of mast cells 33 . In addition, sodium cromolycate has been suggested to stabilize neuronal membranes 34 .…”

Section: Discussionmentioning

confidence: 99%

Mast cell activation in the acupoint is important for the electroacupuncture effect against pituitrin-induced bradycardia in rabbits

Zhu

Wang

Huang

et al. 2017

Sci Rep

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This research was conducted to verify the structural and functional characteristics of mast cells in the electroacupuncture (EA) effects on bradycardia. First, we examined the mast cell density at PC 6, adjacent acupoint LU 7, and a non-acupoint. We tested the effects of EA at PC 6 on heart rate (HR) and blood pressure (BP) in rabbits with pituitrin-induced bradycardia. We also injected sodium cromolyn (Cro), a mast cell membrane stabilizer, at PC 6 30 min before EA to investigate if it affected the EA effects. The results showed that in both PC 6 and LU 7, the mast cell densities were higher than in the non-acupoint (P < 0.05). EA could induce mast cell degranulation at PC 6, which could be suppressed by sodium cromolyn (P < 0.05). EA improved HR, though the change was relatively small in the initial stage with a significant change at 35 min after modelling (P < 0.05). BP significantly improved at 10 min after the onset of pituitrin-induced bradycardia (P < 0.05). The EA effects on both HR and BP were suppressed by sodium cromolyn (P < 0.05). Therefore, we concluded that mast cells in the acupoint are important for the EA effects against pituitrin-induced bradycardia in rabbits.

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Section: Discussionmentioning

confidence: 99%

Mast cell activation in the acupoint is important for the electroacupuncture effect against pituitrin-induced bradycardia in rabbits

Zhu

Wang

Huang

et al. 2017

Sci Rep

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“…In previous reports, it was demonstrated that the new compound 8-hexyloxy-3-(1 H tetrazol-5-yl) -2 H-chromen-2-one (KP-136) is an orally effective antiallergic agent (1), and its mechanism of action depends upon the block of calcium influx that might cause mast cell activation (1,2). The present study describes the antiallergic effects of a principal metabolite of KP-136, 4-[2-oxo-3 (1 H tetrazol 5 yl) -2H -chromen-8-yloxy] butyric acid (C4C) (Fig.…”

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confidence: 99%

Antiallergic effects of 4-(2-oxo-3-(1H-tetrazol-5-yl)-2H-chromen-8-yloxy)-butyric acid.

1989

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Abstract-Antiallergic effects of 4-[2-oxo-3-(1 H-tetrazol-5-yl)-2H-chromen-8 yloxy]-butyric acid (C4C) were studied. C4C is an active principal metabolite of an orally effective antiallergic agent, KP-136. C4C (0.2-1 mg/kg, i.v.) markedly inhibited the mast cell-mediated homologous PCA of rats and the experimental allergic asthma of rats and guinea pigs, although it had almost no effects on he terologous PCA and compound 48/80-induced cutaneous response in rats. C4C (0.2 mg/kg, i.v.) was scarcely effective on cutaneous responses induced by in tradermal injection of histamine and serotonin which are principal chemical mediators of rat homologous PCA, and it blocked the decrease of skin histamine content after the PCA. In addition, C4C (0.01-0.5 ,ug/ml) inhibited the increase of 45Ca uptake of mast cells, the histamine release and the degranulation induced by the antigen antibody interaction. These effects of C4C were much the same as those of KP-136. From the above findings, C4C is considered to be an antiallergic agent that inhibits the mast cell activation by blocking the calcium influx, and it shares similar phar macological properties with KP-136.

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Facile Synthesis of Tetrazolylchromonoids and Related Compounds

Patonay

Lévai

1994

Archiv der Pharmazie

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Einfache Synthese von Tetrazolylchromonoiden und verwandten VerbindungenThe reaction between the appropriate nitriles and tributyltin azide (TBTA) provides an easy and efficient method for the synthesis of the title compounds. Treatment of thiocyanate 9b with TBTA affords the alkylthio-substituted tetrazole lob.Die Umsetzung von Tributylzinnazid (TBTA) mit geeigneten Nitriles stellt eine einfache und ergiebige Methode zur Darstellung der Titelverbindungen dar. Die Behandlung des Rhodanids 9b mit TBTA fiihrt zum substituierten Alkylthiotetrazole lob.Owing to their well-known bioactivities, 5-substituted tetrazoles are especially important products in drug research. They possess, among others, antiallergic'~2), anti asthma ti^^), leukotriene antagonist4). anti-hypertensive5), antithrombotic6), etc. activities. In the course of our work on the synthesis of biologically active chromonoids and 1 -thiochromonoids we aimed to work out a simple and convenient procedure for the preparation of their tetrazolyl derivatives.1,3-Dipolar cycloaddition of azides to nitriles is by far the most widely used method to prepare 5-substituted tetrazoles but it is highly sensitive to the substituents of the substrate, the nature of cation in the azide source and the solvent'). The procedure regarded as the best and used most frequently utilizes in sifu generated NI&NJ in dimethylformamide (DMF)8) but other azide sources have also been d e~e l o p e d~.~) to improve the poor yield of addition to sensitive nitriles. Though the usefulness of TBTA in the synthesis of tetrazoles has been recognizedlO), only scattered applications have been published and the studied substrates, with the exceptions of some peptides"), an enzyme inhibitor'*) or an imidazole derivative") were quite simple.Our interest in the synthesis of tetrazolylchromonoids and -thiochromonoids led us to investigate the reaction of TBTA with various heterocycles having a nitrile function linked directly to either the aromatic or heteroaromatic ring or bridged by an alkoxy chain.Starting materials la-e, 3a-g, and 5 are known (cf. Experimental Part) while hitherto unknown compounds 9a,b were synthesized using standard procedures. Nitrile 9a and chloro compound 8 were obtained by alkylating 7-hydroxy-2-phenyl4H-1 -benzopyran-4-one (7) with 5-chlorovaleronitrile and 1 -bromo-3-chloro-propane, respectively. Treatment of the latter product with KSCN in hot isobutyl methyl ketone afforded thiocyanate 9b in good yield. 2-Aryl-3-cyanobenzopyranones 12a,b were prepared by heating of chloro compounds lla,b with CuCN in N-methyl-2-pyrrolidone (")I4) (Scheme 2). Nitriles la-e, 3a-g, 5, 9a, and 12a,b were reacted with TBTA in refluxing 1,Zdimethoxyethane (DME) or diglyme and the corresponding tetrazoles were obtained (Scheme 1 and 2, Table 1). These solvents seem not to influence the yield, but diglyme allows shorter reaction times because of its higher boiling point. TBTA did affect neither the heterocycles nor the sensitive enone system of compound 3a-g. In

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The protective effect of a new antiallergic agent, KP-136 on mast cell activation: A comparison with disodium cromoglycate

Cited by 10 publications

References 17 publications

Mast cell activation in the acupoint is important for the electroacupuncture effect against pituitrin-induced bradycardia in rabbits

Mast cell activation in the acupoint is important for the electroacupuncture effect against pituitrin-induced bradycardia in rabbits

Antiallergic effects of 4-(2-oxo-3-(1H-tetrazol-5-yl)-2H-chromen-8-yloxy)-butyric acid.

Facile Synthesis of Tetrazolylchromonoids and Related Compounds

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