Effect of NZ-107, a newly synthesized pyridazinone derivative, on antigen-induced contraction of human bronchial strips and histamine release from human lung fragments or leukocytes.
The effects of a newly synthesized pyridazinone derivative, NZ-107, 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone, and two well-known antiasthmatic drugs, amlexanox (orally active disodium cromoglycate-like drug) and disodium cromoglycate (DSCG) on antigen-, histamine- and leukotriene C4 (LTC4)-induced constriction of isolated human tracheal muscle, and histamine release from human lung tissues and leukocytes were investigated in vitro. In some experiments, salbutamol was used as a reference drug. NZ-107 inhibited antigen-, histamine- and LTC4-induced contraction of tracheal muscle. Amlexanox and DSCG did not affect the contractile response of tracheal muscle caused by each stimulant. Salbutamol inhibited antigen-induced contraction of tracheal muscle. NZ-107, amlexanox, DSCG and salbutamol clearly inhibited the antigen-induced release of histamine and LTC4 from human lung tissue. The antigen-induced histamine release from atopic human leukocytes was inhibited by NZ-107 and amlexanox, but not by DSCG. Pretreatment with IL-3 did not alter antigen-induced contraction of tracheal muscle and histamine release from lung tissue, but antigen- or calcium ionophore A 23187-induced histamine release from leukocytes was clearly enhanced. Amlexanox inhibited the IL-3-induced enhancement of histamine release from leukocytes in the case of both stimuli, but NZ-107 and DSCG had no effect. These data suggest that NZ-107 has potent anti-allergic actions based on the inhibition of antigen-induced contraction of human tracheal muscle and mediator release from human lung tissue and leukocytes.
Nagai
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Suda
H
H
Iwama
T
T
Daikoku
M
M
Yanagihara
Y
Y
Koda
A
A
D000631:Aminopyridines / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy; D001980:Bronchi / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects*; D004205:Cromolyn Sodium / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology; D008168:Lung / Q000502:physiology*; D011724:Pyridazines / Q000494:pharmacology*; D013189:SRS-A / Q000494:pharmacology
D000631:Aminopyridines; D007377:Interleukin-3; D011724:Pyridazines; D013189:SRS-A; C062698:NZ 107; D006632:Histamine; C045742:amlexanox; D004205:Cromolyn Sodium