Screening Methods for Anti-Asthmatic Drugs
Pre-clinical In-vitro, Isolated-Organ & In-vivo Animal Models, Endpoints & Reference Drugs
Past RGUHS · 2
RGUHSNov '20
RGUHSNov '17
Introduction & rationale
- Definition — Anti-asthmatic drug screening is the structured pre-clinical evaluation of candidate bronchodilators and anti-inflammatory / anti-allergic agents in in-vitro binding & cell assays, isolated airway-tissue preparations and whole-animal models that reproduce features of human asthma — reversible airflow obstruction, airway inflammation, excess mucus and bronchial hyperresponsiveness (BHR).
- Two therapeutic arms screened separately — Relievers (bronchodilation) — β2-agonists, methylxanthines (theophylline), antimuscarinics (ipratropium) — screened with acute spasmogen-induced bronchoconstriction the test drug must reverse/prevent; controllers (anti-inflammatory) — inhaled corticosteroids, mast-cell stabilisers (cromolyn, nedocromil) — screened with sensitisation–challenge (allergic) models read out by cellular inflammation.
- Why animal models — They let investigators probe asthma/allergy mechanisms and identify novel therapies predictably; no single model equals human disease, so each model's value is judged against its relevance to the human condition.
- Early- + late-phase modelling — Allergic disease has an early phase (immediate bronchoconstriction) and a late phase (cellular infiltration, BHR, remodelling); a validated screening battery includes models of both phases plus a model of increased airway responsiveness.
- Standard drugs anchor every assay — Isoprenaline & aminophylline are relaxant standards in isolated-organ work; spasmogen-matched antagonists (atropine, antihistamine, aminophylline, imipramine) anchor in-vivo screens; cromolyn/nedocromil/dexamethasone anchor mast-cell-dependent endpoints.
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Screening Antiasthmatic Drugs
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