Effect of TYB-2285 on antigen-induced airway responses in sheep

W. M. Abraham, A. Ahmed, A. Cortes, M. Sielczak, A. Wantanabe

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We studied the effect of a new antiallergic compound, TYB-2285 (3,5-bis(acetoxyacetylamino)-4-chlorobenzonitrile), on antigen-induced early and late bronchoconstriction and airway responsiveness in conscious allergic sheep. The same general protocol was used for all studies, except that the dosage and time of TYB-2285 treatment was varied. The basic protocol consisted of determining airway responsiveness to inhaled carbachol, then measuring the airway responses to Ascaris suum antigen challenge followed 1 day later by a post challenge assessment of airway responsiveness. Specific lung resistance (SR(L)) was used to measure the airway responses to antigen and carbachol and the concentration of carbachol that caused a 400% increase in SR(L) (PC400) was used as a measure of airway responsiveness. All protocols were of crossover design, such that each sheep served as its own control and each protocol employed six to eight animals. In all instances, TYB-2285 or vehicle control (methylcellulose) was given orally. When TYB-2285 (100 mg/kg) was given at 16 and 2 h before the challenge, the early response, the late response and the post antigen-induced airway hyperresponsiveness (AHR) as indicated by a decrease in the PC400 was inhibited significantly. TYB-2285 (100 mg/kg), when given 1 h after challenge, inhibited the late response and AHR significantly. TYB-2285 (100 mg/kg), when given 8 h after the challenge, also inhibited the antigen-induced AHR. When animals were given TYB-2285 (100 mg/kg) at 32, 56 and 80 h after the challenge, the antigen-induced AHR that persisted (for 1 week) in the control trial was reversed to the normal level. TYB-2285 (30 mg/kg), when given at 1, 32, 56 and 80 h after the challenge, inhibited late response slightly and reversed the persistent AHR to the normal level. At lower doses (3 and 10 mg/kg) there was no protection of the early response, the late response or AHR. Pretreatment with TYB-2285 (100 mg/kg) also prevented the antigen-induced influx of eosinophils in bronchoalveolar lavage obtained 24 h after segmental antigen challenge. TYB-2285 did not inhibit histamine or LTD4-induced bronchoconstriction nor did the active metabolites of TYB-2285, TC-286 and TC-326 inhibit acetylcholine-induced contraction of sheep tracheal smooth muscle. These results suggest that TYB-2285 has both antiallergic and antiinflammatory properties in the sheep model of allergic bronchoconstriction. The compound demonstrates both prophylactic and therapeutic activity and, therefore, may be potentially useful in the treatment of allergen-induced airway disease.

Original languageEnglish
Pages (from-to)49-58
Number of pages10
JournalPulmonary Pharmacology
Volume9
Issue number1
DOIs
StatePublished - Feb 1 1996
Externally publishedYes

Fingerprint

Sheep
Antigens
Bronchoconstriction
Carbachol
Anti-Allergic Agents
3,5-bis(acetoxyacetylamino)-4-chlorobenzonitrile
Animals
Ascaris suum
Leukotriene D4
Methylcellulose
Bronchoalveolar Lavage
Metabolites
Eosinophils
Allergens
Cross-Over Studies
Histamine
Acetylcholine
Smooth Muscle
Muscle
Anti-Inflammatory Agents

Keywords

  • Airway hyperresponsiveness
  • Animal model
  • Asthma
  • Bronchoconstriction

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pulmonary and Respiratory Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Abraham, W. M., Ahmed, A., Cortes, A., Sielczak, M., & Wantanabe, A. (1996). Effect of TYB-2285 on antigen-induced airway responses in sheep. Pulmonary Pharmacology, 9(1), 49-58. https://doi.org/10.1006/pulp.1996.0006

Effect of TYB-2285 on antigen-induced airway responses in sheep. / Abraham, W. M.; Ahmed, A.; Cortes, A.; Sielczak, M.; Wantanabe, A.

In: Pulmonary Pharmacology, Vol. 9, No. 1, 01.02.1996, p. 49-58.

Research output: Contribution to journalArticle

Abraham, WM, Ahmed, A, Cortes, A, Sielczak, M & Wantanabe, A 1996, 'Effect of TYB-2285 on antigen-induced airway responses in sheep', Pulmonary Pharmacology, vol. 9, no. 1, pp. 49-58. https://doi.org/10.1006/pulp.1996.0006
Abraham WM, Ahmed A, Cortes A, Sielczak M, Wantanabe A. Effect of TYB-2285 on antigen-induced airway responses in sheep. Pulmonary Pharmacology. 1996 Feb 1;9(1):49-58. https://doi.org/10.1006/pulp.1996.0006
Abraham, W. M. ; Ahmed, A. ; Cortes, A. ; Sielczak, M. ; Wantanabe, A. / Effect of TYB-2285 on antigen-induced airway responses in sheep. In: Pulmonary Pharmacology. 1996 ; Vol. 9, No. 1. pp. 49-58.
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