Pharmacological actions of Y-24180: I. A potent and specific antagonist of platelet-activating factor

Terasawa, Michio; Aratani, Hidekazu; Setoguchi, Michihide; Tahara, Tetsuya

doi:10.1016/0090-6980(90)90001-c

Cited by 42 publications

(26 citation statements)

References 28 publications

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“…, is confirmed to show long-acting and potent activities as a PAF antagonist [18,19]. This agent suppresses various PAF-induced reactions both in vivo and in vitro.…”

Section: Introductionmentioning

confidence: 87%

Effects of Y-24180, a Long-Acting and Potent Antagonist to Platelet-Activating Factor, on Immediate Asthmatic Response in Guinea Pigs

Kagoshima¹,

Tomomatsu²,

Iwahisa³

et al. 1997

Pharmacology

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The effect of Y-24180, a potent antagonist to platelet-activating factor (PAF), was evaluated on the antigen-induced immediate asthmatic response (IAR) in actively sensitized guinea pigs that were pretreated with an antihistaminic agent, pyri-lamine. Then, the effect was compared with that of other antiasthmatic agents. In a dose-dependent manner, Y-24180 (0.01–1 mg/kg, p.o.) suppressed the IAR, and WEB 2086 (0.1–10 mg/kg, p.o.), another PAF antagonist, also suppressed IAR in the same fashion as Y-24180. In contrast, AA-2414 (1–100 mg/kg, p.o.), a thromboxane A2 (TXA2) antagonist, was effective only at the beginning of the IAR and ONO-1078 (1–100 mg/kg, p.o.), a peptide leukotriene (pLT) antagonist, was effective only in the latter period, OKY-046, a TXA₂ synthetase inhibitor, showed no significant suppression of the IAR at doses up to 100 mg/kg. Thus, PAF antagonists were more effective than the other agents tested in the present model for IAR. In a subsequent test, Y-24180 (1 mg/kg, p.o.) was confirmed to enhance the suppressive effects of theophylline (10 and 30 mg/kg, p.o.), procaterol (0.1 and 1 µg/kg, i.v.), OKY-046 (100 mg/kg, p.o.) and ONO-1078 (100 mg/kg, p.o.) on the IAR. A combination of three agents, namely Y-24180 with OKY-046 and ONO-1078, completely suppressed the IAR. The results demonstrate that Y-24180 not only suppresses the IAR, but also enhances the suppressive effect of other antiasthmatic agents. Therefore, Y-24180 would be a clinically promising drug for the treatment of bronchial asthma.

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“…, is confirmed to show long-acting and potent activities as a PAF antagonist [18,19]. This agent suppresses various PAF-induced reactions both in vivo and in vitro.…”

Section: Introductionmentioning

confidence: 87%

Effects of Y-24180, a Long-Acting and Potent Antagonist to Platelet-Activating Factor, on Immediate Asthmatic Response in Guinea Pigs

Kagoshima¹,

Tomomatsu²,

Iwahisa³

et al. 1997

Pharmacology

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“…The affinity of Y-24180 for benzodiazepine receptors is lower than those of WEB2086 and etizolam, and is about 1,000 times lower than that for PAF receptors in platelets [15]. Intravenous administration of Y-24180 at doses of 0.3-3 µg·kg -1 causes dose-dependent inhibition of PAF-induced bronchoconstriction in guinea-pigs, but even at a high dose of 10 mg·kg -1 it is either inactive or weakly active against the bronchoconstriction induced by histamine, serotonin, acetylcholine, arachidonic acid, bradykinin, or LTD 4 [21]. In comparison E6123 inhibits PAF inhalation-induced bronchoconstriction in guinea-pigs with a median effective dose (ED50) of 1.3 µg·kg -1 , which is lower than that of Y-24180 (ED50 12 µg·kg -1 ) [22].…”

Section: Discussionmentioning

confidence: 99%

Involvement of PAF in postallergic propranolol-induced bronchoconstriction in guinea-pigs

Fujimura

Tsujiura²,

Songur³

et al. 1996

Eur Respir J

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“…The inhibitory potency of WEB 2086 was weaker than that of Y-24180. Such a pharmacological superiority of Y-24180 over WEB 2086 should also be observed in experiments employing PAF-induced animal models, because a similar kind of difference between these compounds has been reported on models other than the guinea pig model (15)(16)(17). In subsequent experiments, Y-24180 was ascertained to inhibit neither the airway microvascular leakage induced by LTD4 nor that by histamine.…”

Section: Antigen-induced Airway Microvascular Leakagementioning

confidence: 99%

“…As shown in our early papers, Y-24180 is a specific and long-acting PAF-receptor antagonist (15,16), inhibits the vascular leakage induced by PAF in rat skin (17), and also prevents the late asthmatic response and eosinophil recruitment into the airway induced by antigen in guinea pigs (18). In a clinical study, Hozawa et al (19) reported that Y-24180 can reduce bronchial hyperresponsiveness in patients with asthma.…”

mentioning

confidence: 99%

Effect of Y-24180, a Platelet-Activating Factor-Receptor Antagonist, on the Antigen-Induced Airway Microvascular Leakage in Guinea Pigs

Iwahisa¹,

Yamaguchi²,

Kagoshima³

et al. 1996

Japanese Journal of Pharmacology

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ABSTRACT-The inhibitory effect of Y-24180 ((±)-4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H-thieno [3,2-on platelet-activating factor (PAF)-or antigen-induced airway microvascular leakage was studied in guinea pigs by oral administration. The tissue content of extravasated Evans blue dye was used as an index of plasma exudation in the trachea, main bronchi, central intrapulmonary airways and peripheral intrapulmonary airways. In all of these tissues, Y-24180 potently inhibited the leakage induced by PAF. The ED50 value of Y-24180 determined in each of the tissues was approximately 0.02 mg/kg, demonstrating that the inhibitory potency of Y-24180 is 4-6 times that of WEB 2086, another PAF antagonist. Even at a dose of 10 mg/kg, however, Y-24180 showed no inhibitory effect on the leakage induced by leukotriene (LT) D4, histamine or bradykinin. In the antigeninduced model of guinea pigs sensitized with aerosolized ovalbumin, Y-24180 (0.1-10 mg/kg) and WEB 2086 (1-100 mg/kg) potently inhibited the microvascular leakage in all of the examined airway tissues except for the trachea. At 1-100 mg/kg, however, both ONO-1078, an LT-receptor antagonist, and OKY-046, a thromboxane A2 synthetase inhibitor, prevented partially but not significantly the antigen-induced leakage. These results provide evidence that endogenous PAF partially mediates the antigen-induced airway microvascular leakage in guinea pigs.

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Pharmacological actions of Y-24180: I. A potent and specific antagonist of platelet-activating factor

Cited by 42 publications

References 28 publications

Effects of Y-24180, a Long-Acting and Potent Antagonist to Platelet-Activating Factor, on Immediate Asthmatic Response in Guinea Pigs

Effects of Y-24180, a Long-Acting and Potent Antagonist to Platelet-Activating Factor, on Immediate Asthmatic Response in Guinea Pigs

Involvement of PAF in postallergic propranolol-induced bronchoconstriction in guinea-pigs

Effect of Y-24180, a Platelet-Activating Factor-Receptor Antagonist, on the Antigen-Induced Airway Microvascular Leakage in Guinea Pigs

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