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Titolo:
EFFECT OF THE 5-LIPOXYGENASE INHIBITOR ZD2138 ON ALLERGEN-INDUCED EARLY AND LATE ASTHMATIC RESPONSES
Autore:
NASSER SMS; BELL GS; HAWKSWORTH RJ; SPRUCE KE; MACMILLAN R; WILLIAMS AJ; LEE TH; ARM JP;
Indirizzi:
UNITED MED & DENT SCH,GUYS HOSP,DEPT ALLERGY & ALLIED RESP DISORDERS LONDON SE1 9RT ENGLAND UNITED MED & DENT SCH,GUYS HOSP,DEPT ALLERGY & ALLIED RESP DISORDERS LONDON SE1 9RT ENGLAND ZENECA PHARMACEUT MACCLESFIELD CHESHIRE ENGLAND
Titolo Testata:
Thorax
fascicolo: 8, volume: 49, anno: 1994,
pagine: 743 - 748
SICI:
0040-6376(1994)49:8<743:EOT5IZ>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
BRONCHOALVEOLAR LAVAGE FLUID; COMPLEMENT RECEPTOR ENHANCEMENT; URINARY LEUKOTRIENE-E4 LEVELS; BRONCHIAL-ASTHMA; AIRWAY RESPONSES; ATOPIC SUBJECTS; INDUCED BRONCHOCONSTRICTION; LIPOXYGENASE PRODUCTS; ANTIGEN CHALLENGE; HUMAN-NEUTROPHILS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
S.M.S. Nasser et al., "EFFECT OF THE 5-LIPOXYGENASE INHIBITOR ZD2138 ON ALLERGEN-INDUCED EARLY AND LATE ASTHMATIC RESPONSES", Thorax, 49(8), 1994, pp. 743-748

Abstract

Background - Leukotrienes are lipid mediators generated from arachidonic acid by the 5-lipoxygenase pathway which may play an important part in the pathophysiology of asthma. Previous studies have demonstratedattenuation of the allergen-induced early and late asthmatic responses by leukotriene receptor antagonists. The effect of the 5-lipoxygenase inhibitor ZD2138, a non-redox lipoxygenase inhibitor which inhibits leukotriene synthesis for 24 hours after single doses of 350 mg, on allergen-induced early and late asthmatic responses has been assessed. Methods - Eight asthmatic subjects with baseline FEV(1) >70% were studied. On screening, all subjects developed an allergen-induced biphasic asthmatic response to grass pollen, cat dander, or house dust mite. ZD2138 (350mg) or placebo was given on two occasions separated by two weeks in a randomised double blind fashion. Allergen inhalation challenge was performed four hours after dosing and FEV(1) was measured for eight hours. The inhibitory activity of ZD2138 on the 5-lipoxygenase pathway was assessed by measurements of calcium ionophore-stimulated generation of LTB(4) in whole blood ex vivo and by analysis of urinary LTE(4) levels before administration of drug or placebo and at regular intervals after oral drug dosing and allergen challenge. Results - ZD2138produced no significant bronchodilatation or attenuation of the earlyor late asthmatic response, although there was 82% inhibition of whole blood generation of LTB(4) in response to calcium ionophore stimulation and 52% reduction in urinary excretion of LTE(4). Conclusions - Inasthmatic subjects the 5-lipoxygenase inhibitor ZD2138 did not protect against allergen-induced asthmatic responses, despite substantial inhibition of 5-lipoxygenase.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/10/20 alle ore 04:00:21