Disease relevance of 7-[3-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]propoxy]-3,4-dimethyl-4a,8a-dihydrochromen-2-one

• A one-year double-blind clinical study of the efficacy and tolerability of picumast dihydrochloride versus ketotifen in patients with bronchial asthma [1].
• Picumast dihydrochloride's ability to inhibit nasal obstruction after challenge was significantly better than that of placebo in statistical terms [2].
• Pharmacokinetics of picumast dihydrochloride in patients with liver cirrhosis [3].
• Inhibition of the C3-zymosan-induced chemilumiescence of human leucocytes was taken as an indicator of the diminished liberation of mediators and inhibition of the histamine-induced contraction of isolated guinea-pig lung strips as an example for the antagonism of picumast dihydrochloride to mediators of allergic reactions [4].
• After pretreatment of the animals with 3 mg/kg of mepyramine, 10 mg/kg of ketotifen, and 6 mg/kg of picumast dihydrochloride, the inhibitory effect on histamine release from the lung was so marked that both the acute and the protracted anaphylactic shock were completely suppressed [5].

High impact information on 7-[3-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]propoxy]-3,4-dimethyl-4a,8a-dihydrochromen-2-one

• Although results with HEPP have been disappointing, other modulators of mast cell function (e.g. picumast, beta-agonists and phosphodiesterase inhibitors) may prove useful in the future [6].
• Picumast and mast cell function [7].
• The effects of picumast on human eosinophil and neutrophil activation [8].
• CaM antagonism of cloxacepride, picumast, oxatomide, fendiline and bepridil correlated not only with the inhibition of exocytosis evoked by compound 48/80 but also with that induced by A23187, concanavalin A and antigen-IgE [9].
• Compound 48/80-induced histamine release (HR) from the isolated perfused rat heart was markedly and significantly inhibited by picumast (PIC), possibly by acting as a calmodulin antagonist (CMA) or membrane stabilizer [10].

Biological context of 7-[3-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]propoxy]-3,4-dimethyl-4a,8a-dihydrochromen-2-one

• Pharmacokinetics of picumast dihydrochloride and its active metabolites M1 and M2 in humans [11].
• The hydroxylation of picumast was highly saturable, whereas further oxidation was independent of the dose in dogs and only slightly dose-dependent in rats [12].
• The relative bioavailability of picumast dihydrochloride was 20% higher after a meal [11].
• A supplementary in vitro study showed no change in plasma protein binding of picumast (100 ng/ml) in the presence of theophylline (20 micrograms/ml) and vice versa [13].

Anatomical context of 7-[3-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]propoxy]-3,4-dimethyl-4a,8a-dihydrochromen-2-one

• 372 patients with Picumast dihydrochloride- or Ketotifen-treatment regularly underwent ophthalmologic examinations and Scheimpflug photography of the anterior eye segment [14].
• The antagonism of the antiallergic compounds picumast (PIC; Boehringer Mannheim) and ketotifen (K; Sandoz) against pro-allergic mediators like histamine (H), acetylcholine (ACh), SRS-A and LTC4 as well as against the unspecific spasmogen BaCl2 was compared in the bioassay of superfused guinea pig ileum [15].

Associations of 7-[3-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]propoxy]-3,4-dimethyl-4a,8a-dihydrochromen-2-one with other chemical compounds

• Pharmacokinetics of picumast after administration of 14C-picumast dihydrochloride in dogs, rats, rabbits and monkeys [12].
• Effect of picumast on histamine release from rat cardiac and peritoneal mast cells [10].
• A placebo-controlled comparison of the efficacy and tolerability of picumast dihydrochloride and terfenadine in patients with seasonal allergic rhinitis [16].
• Double-blind multicenter controlled clinical study comparing the efficacy of picumast dihydrochloride versus astemizole and placebo in patients with seasonal allergic rhinitis [17].

Analytical, diagnostic and therapeutic context of 7-[3-[4-[(4-chlorophenyl)methyl]piperazin-1-yl]propoxy]-3,4-dimethyl-4a,8a-dihydrochromen-2-one

• A method for determining Picumast, an antiallergic drug, in plasma by HPLC and column switching has been developed [18].
• Lens safety study with Picumast dihydrochloride--a double masked study using the Scheimpflug method [14].
• In a randomized, three-way cross-over study, 12 subjects received at weekly intervals either separated or combined single doses of picumast dihydrochloride (10 mg) and theophylline (7 mg/kg b.w.) Picumast and its metabolites were analysed in plasma and urine up to 24 h and theophylline was assayed in plasma during the same time [13].
• The fraction of the radioactivity in the plasma attributable to the parent compound 0.5 to 3 h after oral administration of picumast dihydrochloride was less than 15% in animals but 95% to 57% in man [4].

References