CR 2039, a new bis-(1H-tetrazol-5-yl)phenylbenzamide derivative with potential for the topical treatment of asthma.
The pharmacological activity of CR 2039 (4-(1H-tetrazol-5-yl)-N-(4-[1H-tetrazol-5-yl]phenylbenzam ide)) a newly discovered antiallergic compound is described. CR 2039 administered i.m. or i.v. inhibited rat passive cutaneous anaphylaxis (PCA) with an ED50 of 0.1 mg/kg and a potency about 15 times higher than that of disodium cromoglycate (DSCG). CR 2039 i.m., by aerosol or as dry powder insufflation, gave dose-related significant protection against IgE-dependent bronchial anaphylaxis induced by aerosolized antigen in anesthetized guinea-pigs. In conscious guinea-pigs CR 2039 given i.m. delayed dose dependently (ED50, 17 mg/kg) the onset of bronchoconstriction induced by aerosolized antigen, while DSCG was ineffective up to 100 mg/kg. The protection was accompanied by significant inhibition of the vascular permeability provoked by antigen challenge in all airway segments except trachea. CR 2039 (10-100 mg/kg i.v.) inhibited the microvascular permeability changes in a model of allergic conjunctivitis in sensitized guinea-pigs. CR 2039 inhibited dose dependently guinea-pig lung cAMP-phosphodiesterase with an IC50 of 50 microM.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000280:Administration, Inhalation; D000707:Anaphylaxis / Q000188:drug therapy; D000818:Animals; D001249:Asthma / Q000188:drug therapy*; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D003233:Conjunctivitis, Allergic / Q000188:drug therapy; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012137:Respiratory System / Q000187:drug effects; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
D001549:Benzamides; D001993:Bronchodilator Agents; D013777:Tetrazoles; C078154:4-(1H-tetrazol-5-yl)-N-(4-(1H-tetrazol-5-yl)phenyl)benzamide; D006632:Histamine; D015105:3',5'-Cyclic-AMP Phosphodiesterases