Bronchodilator and antiallergic properties of LA 2851 (2-4-diamino-7-methyl-pyrazolo (1,5-a) 1,3,5-triazine)

LA 2851, 2-4-diamino-7-methyl-pyrazolo (1,5a) 1, 3, 5 triazine has been found to possess potent bronchodilator and inhibitor properties on experimental active and passive anaphylaxis. In vitro evaluation on guinea-pig trachea indicated that LA 2851 had relaxant properties on unstimulated and stimulated (histamine or pilocarpine) strips. Resistance and compliance measurement in anaesthetized dogs and guinea-pigs showed that the drug reversed or prevented in vivo bronchoconstriction due to histamine. The relaxant effect was not linked to beta stimulating property. LA 2851 was as active as theophylline in all tests used. LA 2851 and theophylline prevented anaphylactic shock in mice. DSCG was poorly active. IgE mediated passive cutaneous anaphylaxis in rat was dose-dependently inhibited by LA 2851 (DSCG greater than LA 2851 greater than theophylline). According to these results the compound decreased histamine release from rat mast cells induced by different secretagogues (LA 2851 greater than DSCG greater than theophylline). No tachyphylaxis (PCA) nor time preincubation dependency (mast cells) was found with LA 2851 as it has been reported for DSCG. LA 2851 by its pharmacological properties associated with a very low toxicity (2.5 to 5 times less than theophylline) provides a new potential agent for respiratory diseases.