Pharmacological studies on BB-1502,a new bronchodilator.

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Abstract
The pharmacological activities of BB 1502 (9-cyclohexyl-2-n-propoxy-9H-adenine), a potent bronchodilator and inhibitor of cAMP phosphodiesterase, were compared with those of aminophylline in a number of biological systems. In vitro, BB 1502 relaxed guinea pig tracheal tissue at a concentration .apprx. 600 times lower than that required for aminophylline. The ability of BB 1502 to inhibit cAMP 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 4-7 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; the potency was 4 times greater than 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.