Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D06123 (Tiacrilast)
 3 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tiacrilast (Ro 22-3747) is an allergic mediator release inhibitor which has demonstrated potent oral activity in two IgE-mediated animal models of immediate hypersensitivity: the rat passive cutaneous anaphylaxis test (ID50 of 0.65 mg/kg) and a model in which anaphylactic bronchospasm is induced in passively sensitized rats (ID50 of 0.022 mg/kg). In addition to oral efficacy, in the latter model Ro 22-3747 was 23-fold more potent than cromoglycate by the aerosol (nebulization) route of administration. In vitro studies have confirmed that the mechanism of action of Ro 22-3747 in the in vivo models is through allergic mediator release inhibition since Ro 22-3747 was a potent inhibitor of antigen-induced (IgE-mediated) histamine release from passively sensitized rat peritoneal cells in vitro (IC50 values of 0.25 and 1.5 microM for Ro 22-3747 and cromoglycate, respectively), and Ro 22-3747 did not display end organ antagonism to histamine, serotonin, or the leukotrienes. Clinical evaluations of Ro 22-3747 at a 350 mg oral dose have been conducted in patients with allergic asthma and allergic rhinitis. In a limited study in allergic asthmatics, Ro 22-3747 demonstrated significant inhibitory activity relative to placebo in reducing acute airway responses to inhaled pollen extracts in patients with ragweed sensitivity (measured by changes in log PD20 FEV1 and log PD35 SGaw). The activity seen, however, was less than that observed with cromoglycate (20 mg) administered by inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pharmacological profile and initial clinical evaluation of tiacrilast (Ro 22-3747): a new antiallergic agent. 242 19

The number of mast cells is increased in psoriatic lesions and this is particularly prominent in their early phase. Mediators released by mast cells may interfere with various aspects of cutaneous inflammation and epidermal proliferation. Therefore, the aim of the present investigation was to find out whether a 4-week treatment period with Tiacrilast, a highly potent inhibitor of mast cell degranulation, might have antipsoriatic potential. A total of 31 patients with plaque-type psoriasis were evaluated after treatment with a 3% Tiacrilast hydrogel and hydrogel alone, in a double-blind, placebo-controlled, within-patient comparative study. No statistically significant improvement of the Tiacrilast-treated plaques compared to the hydrogel-treated sites could be demonstrated. Therefore, the present study does not provide evidence of a potential role of mast cell degranulation in the treatment of psoriasis.
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PMID:Inhibitor of the release of mast cell mediators does not improve the psoriatic plaque. 778 22

Tiacrilast is a potent mast cell degranulation inhibitor in vitro and in animal studies. Since mast cells and their mediators are possibly involved in atopic eczema, we have studied a topically applied 3% hydrogel formulation of tiacrilast against vehicle in a multicenter, double-blind, placebo-controlled trial. Drug or vehicle were applied on involved skin for 28 days. Efficacy was assessed weekly using a 4-point scale for erythema, scaling, induration, exudation and pruritus. An overall assessment of the sites for efficacy and site preference was performed at the end of treatment. In the 32 patients evaluable for efficacy, > 33% improvement was noted on 78% of the drug- and 75% of the vehicle-treated sites, with no statistically significant differences for any of the parameters tested. Treatment was generally well tolerated by all patients. These data suggest that mast cells may not play a major role in the maintenance of atopic eczema lesions.
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PMID:Topical tiacrilast, a potent mast cell degranulation inhibitor, does not improve adult atopic eczema. 810 13