Cloxacepride and related compounds: a new series of orally active antiallergic compounds.
4-[[(p-Chlorophenoxy)acetyl]amino]-5-chloro-2-methoxy-N-[2-(diethylamino)ethyl]benzamide (cloxacepride, 1), exhibited substantial oral antiallergic potential in a reaginic PCA test in rats over a wide range of antigenic challenge times. Available reference compounds with oral activity, such as doxantrazole and 7-(2-hydroxyethoxy)-9-oxoxanthene-2-carboxylic acid (AH 7725, 4), were active only when administered 15 min before challenge: 4, in particular, was not consistent in effect. Oral ED50 values for cloxacepride of 46-49 mg/kg were comparable to that of theophylline and to an intravenous injection of 2 mg/kg of disodium chromoglycate (DSCG) followed by immediate challenge. Following oral ED50 doses, 1 showed slower onset and longer duration of action than theophylline. The absence of inhibition of systemic anaphylaxis and of antihistaminic activity suggests specific effect or reaginic antigen antibody reactions. Structure-activity relationships of various chemical modifications were investigated and discussed in terms of essential substituents.
D000284:Administration, Oral; D000707:Anaphylaxis; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000627:therapeutic use; D005260:Female; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D051381:Rats; D013329:Structure-Activity Relationship; D013806:Theophylline / Q000494:pharmacology
D001549:Benzamides; D006634:Histamine H1 Antagonists; D007202:Indicators and Reagents; D013806:Theophylline; C038348:cloxacepride