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At least 343 records · Page 19Linked to original sources
PubMed1987

Pulmonary aerosol actions of LY188695 (KB2413), a new potent H1-receptor antagonist.

The new potent H1 receptor antagonist, LY188695 (KB2413), was delivered to guinea pigs as a pulmonary aerosol and its ability to inhibit histamine-induced airway obstruction examined. Aerosol LY188695 was more effective than inhaled chlorpheniramine or clemastine in reducing the pulmonary gas trapping produced by histamine challenge. Lung antihistamine effects occurred within minutes of a brief, low concentration aerosol exposure and persisted for at least 1 hour. LY188695 aerosol treatment did not produce significant inhibition of methacholine-induced gas trapping. Although systemic antihistamine effects occurred 50 minutes after LY188695 inhalation, aerosol administration produced an enhanced local (i.e., lung) action compared to intravenous delivery.

Aerosols↗
PubMed1981

Ro 21-7634, a new antiallergic agent with potent oral activity.

Ro 21-7634 was examined for oral antiallergic activity in two in vivo models commonly used to evaluate antiallergics. In the rat PCA test, this drug had an oral ID50 of 1.14 mg/kg and was found to be more potent than several other antiallergics including Disodium Cromoglycate (cromoglycate), Oxatomide, Doxanthrazole, Xanoxate, 2,6-bis (ethyoxyoxalylamino) pyridine, PRD-92-EA and M + B 22,948. In contrast to cromoglycate, Ro 21-7634 was found to be an orally active inhibitor of antigen-induced broncho-constriction in passively sensitized rats (ID50 = 0.2 mg/kg). In addition, Ro 21-7634 inhibited antigen-induced histamine release in an in vivo passive peritoneal anaphylaxis test system, following intraperitoneal administration. Ro 21-7634 demonstrated no end organ antagonism toward histamine, metacholine or serotonin in the guinea pig.

Administration, Oral↗
PubMed1991

BI-L-239, a 5-lipoxygenase inhibitor, blocks inhaled antigen-induced airway hyperresponsiveness in conscious guinea pigs.

Male Hartley guinea pigs were actively sensitized to ovalbumin (OA). Respiratory system resistance (Rrs) was measured by forced oscillations superimposed on tidal breathing. Airway responsiveness (inhaled methacholine PC100) was determined three days prior and three days after (day 10) three alternate day inhalations of OA. Airway cell composition was assessed on day 10 by lung lavage. Three groups (n = 5-6) were studied: A) vehicle challenged, B) OA challenged/placebo treated, C) OA challenged/BI-L-239 (2,6-dimethyl-4-[2-(4-fluorophenyl)ethenyl]phenol) treated (10 x 0.75 mg/actuation, 10 minutes prior to each OA challenge). Animals were treated with pyrilamine and indomethacin (10 mg/kg i.p.) 30 minutes prior to each OA challenge. OA induced acute increases in Rrs of 143 +/- 29%, 238 +/- 73% and 102 +/- 43% in placebo and 86 +/- 34%, 45 +/- 35% (p, 0.05 vs. placebo) and 102 +/- 31% in BI-L-239 treated. OA induced a significant (p less than 0.05) increase in airway leukocytes in placebo (487 +/- 36 to 1615 +/- 421 x 10(3)/ml) but not BI-L-239 treated (to 881 +/- 155 x 10(3)/ml) and decrease in methacholine PC100 in placebo (1.487 +/- 0.49 to 0.39 +/- 0.18 mg/ml) but not BI-L-239 treated (0.99 +/- 34 to 1.04 +/- 0.39 mg/ml). We conclude that BI-L-239 attenuates the airway constriction, inflammation and hyperresponsiveness induced by repeated antigen inhalations in conscious guinea pigs.

Administration, Inhalation↗
PubMed1992

Antigen-induced hyperresponsiveness to methacholine in ventilated, anesthetized guinea pigs.

Guinea pigs were actively sensitized to ovalbumin and exposed 2-3 weeks later to an aerosol of ovalbumin or saline. Changes in lung function were assessed 0.5, 1, 6, 24 and 72 h later by measuring the peak increase in pulmonary inflation pressure induced by i.v. methacholine during constant-volume ventilation. Responses to methacholine were significantly potentiated at 0.5, 1, 6 and 24 h but not at 72 h following exposure to antigen. Hyperresponsiveness to methacholine was maximal at 0.5-1 h and, in terms of magnitude, comparable to the early increase in airway reactivity found in mild asthmatics after allergen challenge. Whether the hyperresponsiveness to methacholine induced by antigen in the guinea pig can be attributed solely to an increase in airway reactivity or is due, at least in part, to decreased lung compliance requires further study.

Aerosols↗
PubMed1992

Multiple antigen challenge produces pulmonary eosinophilia but not pulmonary hyperresponsiveness in actively sensitized guinea pigs.

Exposure of actively sensitized boosted guinea pigs to aerosolized antigen, 3 times on alternate days, produced pulmonary eosinophilia but not pulmonary hyperresponsiveness to methacholine Cl measured 3 days after the last antigen challenge. These data suggest that the presence of large numbers of eosinophils in the airways and tissues of the lungs is not sufficient to produce nonspecific pulmonary hyperresponsiveness. These data also suggest that actively sensitized and boosted guinea pigs respond differently to repeated antigen exposure than do asthmatics or wild caught allergic cynomolgus monkeys.

Aerosols↗
PubMed1992

Comparison of the airway hyperreactivity produced by single and multiple antigen exposures in sensitized guinea pigs.

Chronic airway hyperreactivity is a hallmark feature of asthma, but animal models of airway hyperreactivity often utilize a single antigen challenge. Therefore, we compared the airway hyperreactivity produced by single and multiple antigen challenges in ovalbumin-sensitized guinea pigs. Significant (2-fold) leftward shifts in dose-response curves for i.v. methacholine- or LTD4-induced bronchoconstriction in anesthetized and ventilated animals occurred 24 h following a single ovalbumin challenge. This nonspecific airway hyperreactivity was prevented by pretreatment with ketotifen or dexamethasone. However, airway hyperreactivity was no greater 24 h following the last of 3 daily antigen challenges than after 1 challenge and was absent 72 h following one antigen challenge. These results raise concern over the similarity of antigen-induced airway hyperreactivity in guinea pigs to the chronic airway hyperreactivity in asthmatics.

Animals↗
PubMed1978

Active bronchial anaphylaxis in the rat: inhibition by tiaramide.

Intravenous administration of the benzothiazoline derivative tiaramide hydrochloride, to rats actively sensitized to ovalbumin, inhibited immunologic lung reactions in a dose-related manner. Methysergide also inhibited anaphylactic lung reactions. Serotonin, but not other chemical mediators, produced changes in pulmonary mechanics qualitatively similar to those produced by the sensitizing antigen. The bronchoconstrictive action of serotonin was blocked by methysergide and tiaramide. The latter drug also inhibited bronchoconstriction induced by methacholine. The results implicate serotonin as the primary mediator of the respiratory component of systemic anaphylaxis in the rat: however, the mechanism by which tiaramide inhibits anaphylactic bronchoconstriction remains to be elucidated.

Anaphylaxis↗