Investigational prostaglandin D₂receptor antagonists for airway inflammation

Abstract

Future research should aim to develop once daily compounds and increase the drug clinical potency which, apart from OC000459 and ADC-3680, seems to be relatively low. Further research and development of DP2 receptor antagonists is warranted, particularly in patients with severe uncontrolled asthma, whose management is a top priority. Pediatric studies, which are not available, are required for assessing the efficacy and safety of this novel drug class in children with asthma and allergic rhinitis. Studies on the efficacy of DP2 receptor antagonists in various asthma phenotypes including: smokers, obese subjects, early vs late asthma onset, fixed vs reversible airflow limitation, are required for establishing their pharmacotherapeutic role.

The effect of allergen‐induced bronchoconstriction on concentration of 5‐oxo‐ETE in exhaled breath condensate of house dust mite‐allergic patients

“…Leukotriene B 4 (LTB 4 ), another 5‐LOX product, is chemoattractant to neutrophils . Among COX‐derived prostaglandins, prostaglandin D 2 (PGD 2 ) is a marker of mast cell activation and a potent chemoattractant to eosinophils . Prostaglandin D 2 activates PD2 receptor involved in chemotaxis of lymphocytes, eosinophils and basophils, whereas, bronchoconstrictor activity of PGD 2 and isoprostanes is mediated by thromboxane receptor …”

“…Anti‐inflammatory effects of prolonged therapy with CysLTR 1 antagonists are modest in comparison with inhaled corticosteroids . Studies evaluating effects of PGD 2 antagonists in asthma produced equivocal results …”

“…3,4 Among COX-derived prostaglandins, prostaglandin D 2 (PGD 2 ) is a marker of mast cell activation and a potent chemoattractant to eosinophils. 3,4,10 Prostaglandin D 2 activates PD2 receptor involved in chemotaxis of lymphocytes, eosinophils and basophils, whereas, bronchoconstrictor activity of PGD 2 and isoprostanes is mediated by thromboxane receptor. 3,4,10 In asthmatic patients, the enhanced production of 5-LOX and COX-derived eicosanoids after allergen challenge has been demonstrated using bronchoalveolar lavage (BAL) technique.…”

“…3,4,10 Prostaglandin D 2 activates PD2 receptor involved in chemotaxis of lymphocytes, eosinophils and basophils, whereas, bronchoconstrictor activity of PGD 2 and isoprostanes is mediated by thromboxane receptor. 3,4,10 In asthmatic patients, the enhanced production of 5-LOX and COX-derived eicosanoids after allergen challenge has been demonstrated using bronchoalveolar lavage (BAL) technique. 11 Moreover, locally produced eicosanoids in response to allergen challenge can also be detected in plasma and urine.…”

“…[14][15][16] Studies evaluating effects of PGD 2 antagonists in asthma produced equivocal results. 10 Lipoxygenase and COX metabolites may also down-regulate the asthmatic response. 3,4 Sensitized and exposed to an allergen COX-2 deficient mice are characterized by eosinophil infiltration into bronchial wall and increased production of CysLTs, whilst PGE 2 production is decreased.…”