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Inhibitory effect of aerosol administration of a sulfidopeptide leukotriene antagonist on bronchoconstriction induced by antigen inhalation in guinea pigs.
Arzneimittelforschung. 1994 Jun; 44(6):754-7.A

Abstract

The effects of inhalation of the sulfidopeptide leukotriene antagonist AS-35 (9-[(4-Acetyl-3-hydroxy-2-n-propyl-phenoxy)methyl]-3-(1H- tetrazol-5-yl)-4H-pyrido [1,2-a]pyrimidin-4-one, CAS 108427-72-1) on bronchoconstriction induced by aerosol antigen, histamine, and leukotriene C4, D4 (LTC4, D4) were investigated in anesthetized and artificially ventilated guinea pigs. The increase in pressure at the airway opening (P(ao)) was measured as an index representing the grade of bronchial response. The bronchoconstriction induced by aerosol antigen was suppressed dose-dependently by pretreatment with inhaled AS-35 (0.1 mg and 1 mg) through a pressurized meter-dosed inhaler in the passively sensitized animals pretreated with diphenhydramine hydrochloride. But the histamine-induced bronchoconstriction was not altered by the pretreatment with AS-35 inhalation. On the other hand, LTC4- and LTD4-induced bronchoconstriction was inhibited by the pretreatment with aerosol AS-35 in a dose-dependent manner. The deposited dose of inhaled AS-35 in the peripheral airways was 3.5 micrograms and 6.5 micrograms when 0.1 mg and 1 mg of the drug was inhaled, respectively. These results suggest that sulfidopeptide leukotrienes (s-LTs) play an important role in the allergic bronchoconstriction in guinea pigs pretreated with antihistamine, and AS-35 inhalation may be beneficial in the treatment of asthma.

Authors+Show Affiliations

Third Department of Internal Medicine, Kanazawa University School of Medicine, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8053975

Citation

Bando, T, et al. "Inhibitory Effect of Aerosol Administration of a Sulfidopeptide Leukotriene Antagonist On Bronchoconstriction Induced By Antigen Inhalation in Guinea Pigs." Arzneimittel-Forschung, vol. 44, no. 6, 1994, pp. 754-7.
Bando T, Fujimura M, Shintani H, et al. Inhibitory effect of aerosol administration of a sulfidopeptide leukotriene antagonist on bronchoconstriction induced by antigen inhalation in guinea pigs. Arzneimittelforschung. 1994;44(6):754-7.
Bando, T., Fujimura, M., Shintani, H., Saito, M., Kurashima, K., Nishi, K., & Matsuda, T. (1994). Inhibitory effect of aerosol administration of a sulfidopeptide leukotriene antagonist on bronchoconstriction induced by antigen inhalation in guinea pigs. Arzneimittel-Forschung, 44(6), 754-7.
Bando T, et al. Inhibitory Effect of Aerosol Administration of a Sulfidopeptide Leukotriene Antagonist On Bronchoconstriction Induced By Antigen Inhalation in Guinea Pigs. Arzneimittelforschung. 1994;44(6):754-7. PubMed PMID: 8053975.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibitory effect of aerosol administration of a sulfidopeptide leukotriene antagonist on bronchoconstriction induced by antigen inhalation in guinea pigs. AU - Bando,T, AU - Fujimura,M, AU - Shintani,H, AU - Saito,M, AU - Kurashima,K, AU - Nishi,K, AU - Matsuda,T, PY - 1994/6/1/pubmed PY - 1994/6/1/medline PY - 1994/6/1/entrez SP - 754 EP - 7 JF - Arzneimittel-Forschung JO - Arzneimittelforschung VL - 44 IS - 6 N2 - The effects of inhalation of the sulfidopeptide leukotriene antagonist AS-35 (9-[(4-Acetyl-3-hydroxy-2-n-propyl-phenoxy)methyl]-3-(1H- tetrazol-5-yl)-4H-pyrido [1,2-a]pyrimidin-4-one, CAS 108427-72-1) on bronchoconstriction induced by aerosol antigen, histamine, and leukotriene C4, D4 (LTC4, D4) were investigated in anesthetized and artificially ventilated guinea pigs. The increase in pressure at the airway opening (P(ao)) was measured as an index representing the grade of bronchial response. The bronchoconstriction induced by aerosol antigen was suppressed dose-dependently by pretreatment with inhaled AS-35 (0.1 mg and 1 mg) through a pressurized meter-dosed inhaler in the passively sensitized animals pretreated with diphenhydramine hydrochloride. But the histamine-induced bronchoconstriction was not altered by the pretreatment with AS-35 inhalation. On the other hand, LTC4- and LTD4-induced bronchoconstriction was inhibited by the pretreatment with aerosol AS-35 in a dose-dependent manner. The deposited dose of inhaled AS-35 in the peripheral airways was 3.5 micrograms and 6.5 micrograms when 0.1 mg and 1 mg of the drug was inhaled, respectively. These results suggest that sulfidopeptide leukotrienes (s-LTs) play an important role in the allergic bronchoconstriction in guinea pigs pretreated with antihistamine, and AS-35 inhalation may be beneficial in the treatment of asthma. SN - 0004-4172 UR - https://www.unboundmedicine.com/medline/citation/8053975/Inhibitory_effect_of_aerosol_administration_of_a_sulfidopeptide_leukotriene_antagonist_on_bronchoconstriction_induced_by_antigen_inhalation_in_guinea_pigs_ L2 - https://www.lens.org/lens/search?q=citation_id:8053975 DB - PRIME DP - Unbound Medicine ER -