Apafant (a PAF receptor antagonist) suppresses the early and late airway responses in guinea pigs: a comparison with antiasthmatic drugs.
We studied the effects of apafant (WEB 2086 BS), a specific and potent platelet activating factor (PAF) receptor antagonist, on the early and late airway responses in conscious and actively sensitized guinea pigs. An increase in airway resistance (Rs) was seen 1 min after the inhaled antigen challenge (early airway response), followed by another increase in Rs which peaked between 4 and 8 h after the provocation (late airway response). Oral administration of apafant as well as theophylline inhibited both early and late airway responses. Ozagrel, an inhibitor of thromboxane A2 synthetase, salbutamol, a beta2-adrenoceptor agonist, and dexamethasone significantly inhibited either the early or the late airway response only. Disodium cromoglycate inhibited neither the early nor the late airway response. The results showed that apafant inhibited both the early and late airway responses in sensitized guinea pigs and its effect was comparable or superior to that of anti-asthmatic drugs used clinically.
Ikegami
K
K
Department of Pharmacology, Kawanishi Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd., Yato, Japan.
Hata
H
H
Fuchigami
J
J
Tanaka
K
K
Kohjimoto
Y
Y
Uchida
S
S
Tasaka
K
K
D000280:Administration, Inhalation; D000284:Administration, Oral; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects*; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D004205:Cromolyn Sodium / Q000008:administration & dosage / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D004347:Drug Interactions; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D008689:Methacrylates / Q000008:administration & dosage / Q000494:pharmacology; D008797:Metyrapone / Q000008:administration & dosage / Q000494:pharmacology; D010047:Ovalbumin / Q000008:administration & dosage / Q000633:toxicity; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010991:Plethysmography; D011738:Pyrilamine / Q000008:administration & dosage / Q000494:pharmacology; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014611:Vaccination
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D001381:Azepines; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D008689:Methacrylates; D010975:Platelet Aggregation Inhibitors; D014230:Triazoles; C052518:WEB 2086; D003907:Dexamethasone; D010047:Ovalbumin; D013806:Theophylline; D013930:Thromboxane-A Synthase; D011738:Pyrilamine; C034364:ozagrel; D004205:Cromolyn Sodium; D000420:Albuterol; D008797:Metyrapone