Effects of NIP-502 on Antigen-Induced Bronchial Responses and Allergic Reactions in Animal Models

Abstract

ABSTRACT-We examined the effect of a newly synthesized pyridazinone derivative, NIP-502 [4-chloro-5-(3-ethoxy)-4-phenoxybenzamine)-3(2H)-pyridazinone], on antigen-induced bronchial responses and allergic reactions in several animal models. NIP-502 (10 mg/kg, p.o.) inhibited the antigen-induced immediate asthmatic response in passively sensitized guinea pigs. The inhibitory effect was also observed in metyrapone (an inhibitor of 11(3-hydroxylase)-pretreated guinea pigs. NIP-502 improved ovalbumin (OA)-induced airway hyperresponsiveness to acetylcholine and inhibited the OA-induced increase in the number of inflammatory leukocytes in the bronchoalveolar lavage fluid. These inhibitory effects on OA-induced responses were similar to those of prednisolone. NIP-502 also showed an inhibitory effect on the passive cutaneous anaphylactic reaction in rats but did not inhibit the reversed cutaneous anaphylactic reaction, reversed Arthus reaction or delayed type hypersensitivity reaction. On the other hand, prednisolone showed broad inhibitory effects except for the reversed cutaneous anaphylactic reaction. In the in vitro study, NIP-502 (30 pM) significantly inhibited Formyl-Met-Leu-Phe-induced superoxide anion production by the guinea pig alveolar macrophages. These results indicate that the inhibitory effects of NIP-502 on bronchial responses are similar to those of prednisolone, but this compound seemed to act more selectively on the respiratory tract than prednisolone. Because of its effectiveness against a variety of bronchial responses, NIP-502 may be useful in the treatment of bronchial asthma.

The Difference in Citric Acid-Induced Cough in Congenitally Bronchial-Hypersensitive (BHS) and Bronchial-Hyposensitive (BHR) Guinea Pigs.

“…Airway hypersensitivity is considered as the most fundamental and common factor in the elicitation of asthma [25,32], which shows an exaggerated bronchoconstrictive response to various non-specific stimuli as well as specific agents such as histamine and acethylcholine. In patients with asthmatic attack, cough is the most common symptom and is normally accompanied by the occurrence of severe bronchoconstriction [23].…”

“…However, the higher elicitation of cough in asthmatic patients might be produced not only by the higher responsiveness of airway receptors but also by many other factors such as dysfunction of the autonomic nervous system and humoral influence on the airway. Several kinds of model animals have been used to examine the relationship between airway responsiveness and cough, such as Ascaris suum-sensitized guinea pigs [16], cigarette smoke-sensitized guinea pigs [14], metyrapone and ovalbumin-sensitized guinea pigs [32]. BHS (bronchial-hypersensitive) and BHR (bronchial-hyposensitive) strain guinea pigs are spontaneous model animals of airway hyper-and hyposensitivity [22].…”

Synthesis and Applications of Pyridazinones for Base oil Improvement

“…It's well-known and found out the important the 6-ary l pyridazin-3(2H)-one in med icinal fields [22][23][24][25][26][27][28]. The newly route apply and study the target compounds in petro chemistry as antioxidant, and anti-corrosion additives.…”

“…Beside, they are active as antifungal, antibacterial, antiv iral, anti-inflammatory, vasodilation, and anticonvulsant [20][21][22][23][24][25]. Pyridazinone derivatives incorporated with diazole mo ieties that exhib it b iological activ ity agents, (Emo rfazone and related compounds) [26], for therapeutic intervention of renal urologic [27], respiratory (NIP-502) [28] and dermatolog ic diseases (FR-1818177) [29] and pyridazinone, (PDE inhibitor developers) [30]. The design of newly prepared co mpounds based on the structure containing other biological actives heterocycles on the side chains [31].…”

Anti-asthma effect of an antiviral drug, acyclovir: a clinical case and experimental study

“…As an index of airway obstruction, the ratios of expiration time to inspiration time (E/1) were assessed according to the methods previously described [7]. E/I ratio was expressed as the mean of 10 waves ofthe respiratory curve, and all data were expressed as % change from E/I at the pre*inhalation period.…”