A comparative study of the respiratory responses to bronchoactive agents in rhesus and cynomolgus monkeys.

Respiratory responses to a variety of known bronchoactive agents were compared in anesthetized rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) monkeys. Administration of 0.1 to 1.0% histamine aerosols resulted in an increase in airway resistance of 50 to 200% and a decrease in lung compliance of 30 to 80%. Aerosols of prostaglandin E2 (1 mg/ml), terbutaline (10 mg/ml), and isoproterenol (10 mg/ml) or iv aminophylline (up to 7.0 mg/kg) administered concomitantly with histamine produced a transient reversal of the histamine-induced changes in both species. Since the rhesus and cynomolgus monkeys responded in a comparable manner to these bronchodilator agents, the cynomolgus monkey appears to be an additional valuable model for the evaluation of potential bronchoactive compounds.

Evaluation of rotenone and related compounds as antagonists of slow-reacting substance of anaphylaxis.

Rotenone (1), dihydrorotenone (2), isorotenone (3), mutarotenone (4), and deguelin (12) were found to be potent antagonists of slow-reacting substance of anaphylaxis (SRS-A) in vitro. However, these compounds were also shown to inhibit histamine, serotonin, and acetylcholine at only ten times their IC50 concentrations for SRS-A antagonism. Rotenone (1) and several related compounds were also evaluated in an in vivo guinea pig anaphylaxis model. Several of these compounds and FPL 55712 (I) were effective in prolonging collapse times of animals which received an aerosol challenge of an antigen to which they had been sensitized.