title: Pharmacological studies on BB-1502, a new bronchodilator.
abstract: The pharmacological activities of BB-1502 (9-cyclohexyl-2-n-propoxy-9H-adenine), a potent bronchodilator and inhibitor of cyclic AMP phosphodiesterase, were compared with those of aminophylline in a number of biological systems. IOn vitro, BB-1502 relaxed guinea pig tracheal tissue at a concentration ca. 600 times lower than that required for aminophylline. The ability of BB-1502 to inhibit cyclic AMP phosphodiesterase of guinea pig lung origin was 15 times greater than that of aminophylline. The direct bronchodilator activity of BB-1502 determined in guinea pigs by the intraduodenal route was 5 times greater and the duration of the action longer than that of aminophylline. In dogs, intraduodenal BB-1502 inhibited bronchoconstriction induced by pilocarpine, histamine, or acetylcholine and the activity of the new compound was 4 to 7 times more potent than that of aminophylline. In experimental asthma studies, orally administered BB-1502 protected guinea pigs from allergy-induced asthma provoked by an antigen challenge with aerosolized egg albumin and here the potency was 4 times greater that that of aminophylline. Ascaris antigen-induced asthma in dogs was completely inhibited by the oral administration of BB-1502 in a dose of 1 mg/kg with significant protection seen at 0.3 and 0.1 mg/kg. No complete protection was obtained with aminophylline in the dog asthma model. Cardiovascular effects observed with guinea pigs and dogs following the oral administration of BB-1502 were considerably less than those seen with aminophylline. CNS side effects were nil in rats when BB-1502 was given at 3 times the dose that produced significant stimulation by aminophylline. Acute lethal toxicity determined in mice by the oral route was similar for BB-1502 and aminophylline.
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000517:prevention & control; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002319:Cardiovascular System / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014132:Trachea / Q000187:drug effects
chemical_list: D001993:Bronchodilator Agents; D006633:Histamine Antagonists; D010862:Pilocarpine; D000628:Aminophylline; C032993:9-cyclohexyl-2-n-propoxy-9H-adenine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000225:Adenine; D000109:Acetylcholine