CR 2039, a new bis-(1H-tetrazol-5-yl)phenylbenzamide derivative with potential for the topical treatment of asthma

  • Eur J Pharmacol. 1992 Dec 8;229(1):45-53. doi: 10.1016/0014-2999(92)90284-b.
L Revel  1 ,  S Colombo ,  F Ferrari ,  G Folco ,  L C Rovati ,  F Makovec
Affiliations
  • 1. Rotta Research Laboratorium, Monza, Milano, Italy.
PMID: 1282105 DOI: 10.1016/0014-2999(92)90284-b
Abstract

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.

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