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.