Twenty‐first century mast cell stabilizers

Abstract

Mast cell stabilizing drugs inhibit the release of allergic mediators from mast cells and are used clinically to prevent allergic reactions to common allergens. Despite the relative success of the most commonly prescribed mast cell stabilizer, disodium cromoglycate, in use for the preventative treatment of bronchial asthma, allergic conjunctivitis and vernal keratoconjunctivitis, there still remains an urgent need to design new substances that are less expensive and require less frequent dosing schedules. In this regard, recent developments towards the discovery of the next generation of mast cell stabilizing drugs has included studies on substances isolated from natural sources, biological, newly synthesized compounds and drugs licensed for other indications. The diversity of natural products evaluated range from simple phenols, alkaloids, terpenes to simple amino acids. While in some cases their precise mode of action remains unknown it has nevertheless sparked interest in the development of synthetic derivatives with improved pharmacological properties. Within the purely synthetic class of inhibitors, particular attention has been devoted to the inhibition of important signalling molecules including spleen TK and JAK3. The statin class of cholesterol-lowering drugs as well as nilotinib, a TK inhibitor, are just some examples of clinically used drugs that have been evaluated for their anti-allergic properties. Here, we examine each approach under investigation, summarize the test data generated and offer suggestions for further preclinical evaluation before their therapeutic potential can be realized.

Inhibitory effect of a new orally active cedrol-loaded nanostructured lipid carrier on compound 48/80-induced mast cell degranulation and anaphylactic shock in mice

“…Agents that prevent Ca 2+ mobilization across the membrane and mediator release from mast cells are termed as mast cell stabilizers. 84 Compound 48/80 is well known for its ability to induce anaphylactic reaction by releasing mediator from mast cell. 85 The present study has demonstrated that cedrol and CR-NLCs inhibit compound 48/80-induced systemic anaphylaxis-like reactions in mice (Table 7).…”

About High Potent Efficacy of FLEBIL in Pharmacotherapy of Hemorrhoidal Disease Associated with Irritable Bowel Syndrome (IBS)

“…It has been identified potent mast cells stabilizer effect of natural components (flavonoids, phenols, terpenoids, coumarins) [4,5]. Furthermore considerable non-gastrointestinal symptoms are typical for IBS as well.…”

“…Particularly, flavonoids express mast cells stabilizer effect, exactly among them are quercetin, rutin, fisetin, kaempferol. Furthermore quercetin decreases IL-1b, IL-6, IL-8 and TNF production and more effectively inhibits cytokines release from human mast cells, than mast cells well known stabilizer cromolyn [4][5][6][7].…”

Occupational Contact Dermatitis Due to Acrylates and Methacrylates

“…Various receptors and signaling proteins are then activated which leads to distinct signaling pathways, all part of a signaling cascade. Subsequent activation leads to the release of granule-associated mediators and lipid-derived mediators such as prostaglandins and leukotrienes and the synthesis of cytokines and chemokines which provoke instantaneous and chronic allergic inflammation (Metcalfe et al 1997;Finn and Walsh 2013). Mast cell stabilizers work by inhibiting the release of allergic mediators from mast cells and are mainly used clinically to prevent allergic reactions caused by common allergens.…”