BIOMAT Database Logo BIOMAT Database Logo

Activity of a novel thienodiazepine derivative as a platelet-activating factor antagonist in guinea pig lungs. Effects on platelet-activating factor and allergen induced eosinophil accumulation. 1991

H Tsunoda, and Y Sakuma, and M Shirato, and H Obaishi, and K Harada, and K Yamada, and N Shimomura, and Y Machida, and I Yamatsu, and K Katayama
Allergy and Asthma Research Unit, Eisai Co., Ltd., Ibaraki, Japan.

Platelet-activating factor (PAF) inhalation in guinea pigs caused a significant increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). Oral administration of (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123), a novel PAF antagonist, at the dose of 100 micrograms/kg completely inhibited the PAF-induced eosinophil accumulation. Antigen inhalation in passively sensitized guinea pigs caused a significant increase in lung contents of PAF at 5 min, and accumulation of eosinophils in the bronchi 1 and 2 days thereafter, E-6123 inhibited the antigen-induced eosinophil accumulation and the maximum inhibition was approximately 65%. On the other hand, methylprednisolone completely inhibited the antigen-induced eosinophil accumulation. The results suggest that PAF is a potent attractant of eosinophils and is involved in antigen-induced eosinophil infiltration into bronchi. The results also suggest that E-6123 may be of therapeutic value in the treatment of asthma exhibiting eosinophil recruitment in airways.

UI MeSH Term Description Entries
D007958 Leukocyte Count The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells. Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D008775 Methylprednisolone A PREDNISOLONE derivative with similar anti-inflammatory action. 6-Methylprednisolone,Medrol,Metipred,Urbason,6 Methylprednisolone
D010972 Platelet Activating Factor A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION. AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D001992 Bronchoalveolar Lavage Fluid Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung. Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D004804 Eosinophils Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. Eosinophil
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000336 Aerosols Colloids with a gaseous dispersing phase and either liquid (fog) or solid (smoke) dispersed phase; used in fumigation or in inhalation therapy; may contain propellant agents. Aerosol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

H Tsunoda, and Y Sakuma, and M Shirato, and H Obaishi, and K Harada, and K Yamada, and N Shimomura, and Y Machida, and I Yamatsu, and K Katayama
Bronchoconstriction and eosinophil recruitment in guinea pig lungs after platelet activating factor administration.
January 1997, The Journal of asthma : official journal of the Association for the Care of Asthma,
H Tsunoda, and Y Sakuma, and M Shirato, and H Obaishi, and K Harada, and K Yamada, and N Shimomura, and Y Machida, and I Yamatsu, and K Katayama
Dual effects of a novel thienodiazepine platelet-activating factor antagonist, on drug-oxidizing enzymes in beagle dog.
April 1994, Xenobiotica; the fate of foreign compounds in biological systems,
H Tsunoda, and Y Sakuma, and M Shirato, and H Obaishi, and K Harada, and K Yamada, and N Shimomura, and Y Machida, and I Yamatsu, and K Katayama
Interspecies scaling of a thienodiazepine platelet-activating factor receptor antagonist.
July 1995, Drug metabolism and disposition: the biological fate of chemicals,
H Tsunoda, and Y Sakuma, and M Shirato, and H Obaishi, and K Harada, and K Yamada, and N Shimomura, and Y Machida, and I Yamatsu, and K Katayama
Effects of a potent platelet-activating factor antagonist, SR27417A, on allergen-induced asthmatic responses.
July 1997, American journal of respiratory and critical care medicine,
H Tsunoda, and Y Sakuma, and M Shirato, and H Obaishi, and K Harada, and K Yamada, and N Shimomura, and Y Machida, and I Yamatsu, and K Katayama
Pentoxifylline attenuates platelet activating factor-induced permeable edema in isolated perfused guinea pig lungs.
May 1994, Zhongguo yao li xue bao = Acta pharmacologica Sinica,
H Tsunoda, and Y Sakuma, and M Shirato, and H Obaishi, and K Harada, and K Yamada, and N Shimomura, and Y Machida, and I Yamatsu, and K Katayama
[Effect of platelet-activating factor on nasal vascular permeability and eosinophil accumulation in guinea pigs].
April 1990, Nihon Jibiinkoka Gakkai kaiho,
H Tsunoda, and Y Sakuma, and M Shirato, and H Obaishi, and K Harada, and K Yamada, and N Shimomura, and Y Machida, and I Yamatsu, and K Katayama
Inhibitory effects of a novel platelet activating factor (PAF) antagonist (BN 52021) on antigen-induced prostaglandin and thromboxane formation by the guinea pig lung.
August 1986, Pharmacological research communications,
H Tsunoda, and Y Sakuma, and M Shirato, and H Obaishi, and K Harada, and K Yamada, and N Shimomura, and Y Machida, and I Yamatsu, and K Katayama
Effects of selective phosphodiesterase inhibitors on platelet-activating factor- and antigen-induced airway hyperreactivity, eosinophil accumulation, and microvascular leakage in guinea pigs.
January 1996, Naunyn-Schmiedeberg's archives of pharmacology,
H Tsunoda, and Y Sakuma, and M Shirato, and H Obaishi, and K Harada, and K Yamada, and N Shimomura, and Y Machida, and I Yamatsu, and K Katayama
[Effects of a platelet-activating factor antagonist ONO-6240 on antigen induced eosinophil infiltration into the airways].
November 1995, Zhonghua nei ke za zhi,
H Tsunoda, and Y Sakuma, and M Shirato, and H Obaishi, and K Harada, and K Yamada, and N Shimomura, and Y Machida, and I Yamatsu, and K Katayama
The anaphylactic release of platelet-activating factor from perfused guinea-pig lungs.
May 1986, British journal of pharmacology,
Copied contents to your clipboard!