Pharmacological studies on BB-1502, a new bronchodilator

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.