title: New pharmacological data on the bronchospasmolytic activity of bamifylline.
abstract: Resistance to lung inflation and blood pressure were monitored together with biological and radioimmunological determination of circulating thromboxane A2 (TxA2) in anaesthetized guinea-pig. Bamifylline, a 2-benzyl-[4,5-d]-imidazopyrimidine derivative, and theophylline were compared for their antagonistic activity against the pulmonary effect of histamine (0.05 mumol/kg i.v.), leukotriene C4 (LTC4, 0.016 mumol/kg i.v.), platelet-activating factor (PAF, 0.0002 mumol/kg i.v.) and acetylcholine (0.1 mumol/kg i.v.). Bamifylline, as well as theophylline, showed a dose-dependent antagonistic activity against both bronchoconstriction and TxA2 generation induced by the above agonists. However, except for histamine where the two compounds were equiactive, bamifylline was 2 times more potent than theophylline. The maximal inhibitory activity was found against bronchoconstriction induced by PAF (ED50 = 6.5 mumol/kg i.v.) followed by histamine (ED50 = 9.5 mumol/kg i.v.), acetylcholine (ED50 = 24.3 mumol/kg i.v.) and LTC4 (ED50 = 31.6 mumol/kg i.v.). Bamifylline (3, 10, 30, 100 mumol/kg i.v.) and theophylline (3, 10, 30, 100 mumol/kg i.v.) protected guinea-pig from antigen-induced bronchoconstriction and TxA2 generation in ovalbumin actively sensitized animals. Also in this series of experiments bamifylline was more potent than theophylline, the ED50 being 9.3 mumol/kg i.v. and 22.9 mumol/kg i.v., respectively. These pharmacological data represent new support for the protecting effect of bamifylline against respiratory damage induced by well known anaphylaxis mediators.
authors: Institute of Pharmacological Sciences, University of Milan, Italy.
authors: F
authors: F
authors: Berti
authors: F
authors: F
authors: Magni
authors: G
authors: G
authors: Rossoni
authors: P
authors: P
authors: Schiantarelli
authors: S
authors: S
authors: Bongrani
authors: R
authors: R
authors: Pasargiklian
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects; D000707:Anaphylaxis / Q000503:physiopathology; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology; D013189:SRS-A / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism
chemical_list: D001993:Bronchodilator Agents; D010972:Platelet Activating Factor; D013189:SRS-A; D013928:Thromboxane A2; D006632:Histamine; D013806:Theophylline; D000109:Acetylcholine; C006683:bamifylline