Thromboxane A(2) is a novel endogenous secretagogue of Cl(-) secretion in the distal colon. Here, we examined if the Cl(-) secretion caused by platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is mediated by thromboxane A(2) production using isolated mucosae of the rat colon. Furosemide (100 microM) and 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB; 300 microM) completely inhibited PAF (10 microM)-induced increase in short-circuit current (Isc) across the mucosa, indicating that PAF caused a Cl(-) secretion in the rat colon. A selective thromboxane A(2) receptor antagonist (sodium(E)-11-[2-(5, 6-dimethyl-1-benzimidazolyl)-ethylidene]-6,11-dihydrobenz[b, e]oxepine-2-carboxylate monohydrate; KW-3635), and a selective thromboxane synthase inhibitor (sodium 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3, 5-dimethylbenzoate dihydrate; Y-20811) inhibited the PAF-induced Cl(-) current in a concentration-dependent manner. The IC(50) values of KW-3635 and Y-20811 were 2.1 and 0.5 microM, respectively. 30 microM KW-3635 and 1 microM Y-20811 inhibited the PAF response by 92% and 83%, respectively. These inhibitors did not affect the prostaglandin E(2)-induced increase in Isc. A 5-lipoxygenase-activating protein inhibitor (3-[1-(p-chlorobenzyl)-5-(isopropyl)-3-t-butylthioindol-2-yl]-2, 2-dimethyl-propanoic acid sodium; MK-886) (5 microM) did not affect the PAF-induced Cl(-) current. The present study suggests that the PAF-induced Cl(-) secretion in the rat colonic mucosa is mainly mediated by a release of thromboxane A(2).

01 Jan 1994·Folia Pharmacologica Japonica

Effect of Y-20811, a thromboxane A2 synthetase inhibitor, on the arachidonic acid-induced response in the blood-superfused canine coronary artery.

Article

Author: Noguchi, Yutaka ; Inui, Jun ; Matsumoto, Yasuhiro

Effects of Y-20811, a thromboxane A2 synthetase inhibitor, on the arachidonic acid (AA)-induced responses were investigated in the isolated canine coronary artery superfused with blood from a donor dog and Krebs-Henseleit solution. When the coronary artery was superfused with Krebs-Henseleit solution, AA did not have any remarkable effect on its tone. In the coronary artery superfused with blood, in contrast, AA (10-100 micrograms) caused phasic constriction followed by relaxation. After denudation of the endothelium, the contractile response was augmented, and the relaxant effect was abolished. Y-20811 (1 mg/kg, i.v.), administered into the donor dog, inhibited the contraction and augmented the relaxation. Indomethacin (5 mg/kg, i.v.) and aspirin (30 mg/kg, i.v.) also inhibited the AA-induced contraction. However, indomethacin inhibited the relaxation induced by AA (10-100 micrograms), whereas aspirin inhibited the relaxation induced by a low dose of AA (10-30 micrograms). These results suggest that Y-20811 inhibits the TXA2-induced contraction and augments the production of the relaxant metabolite of AA in the coronary artery.

01 Oct 1993·European Archives of Oto-Rhino-LaryngologyQ3 · MEDICINE

Role of thromboxane A2 in a microcirculation disorder of the rat inner ear

Q3 · MEDICINE

Article

Author: Y. Asai ; K. Umemura ; T. Uematsu ; M. Nakashima

Since thromboxane (TX) A2 causes vasoconstriction and platelet aggregation, we evaluation the effect of a TXA2 receptor antagonist (vapiprost) and a TXA2 synthetase inhibitor (Y-20811) on a microcirculation disorder in the rat inner ear that was induced by a photochemical reaction between an intravenous injection of rose bengal (RB) and green light. A gradual decrease of the cochlear action potential (CAP) to an 8 kHz sound stimulus was measured with an electrocochleogram and occurred after the RB injection. The CAP then disappeared 5 min after the injection of RB. Both vapiprost and Y-20811 significantly prolonged the time required to complete suppression of the CAP as compared with saline as control. These findings indicate that TXA2 may play an important role in microcirculation disorders in the rat inner ear.

100 Deals associated with Y-20811

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Arrhythmias, Cardiac	Phase 3	JP	Mitsubishi Pharma Corp.	-
Asthma	Phase 3	-	Mitsubishi Tanabe Pharma Corp.	-
Myocardial Ischemia	Phase 3	JP	Mitsubishi Pharma Corp.	-
Thrombosis	Phase 3	-	Mitsubishi Tanabe Pharma Corp.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

Y-20811

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation