Assessment of β‐adrenergic receptor blockade after isamoltane, a 5‐HT 1 ‐receptor active compound, in healthy volunteers

This study investigated the effects of isamoltane on the changes induced by cumulative doses of inhaled albuterol (salbutamol) on bronchomotor tone, skeletal muscle, circulatory system, and metabolism after single (day 1) and multiple dosing (day 7) in 15 healthy subjects. The volunteers were given placebo, 4 mg isamoltane, 10 mg isamoltane, or 20 mg propranolol over a 7‐day period in a randomized, double‐blind, crossover design. The greatest attenuation in albuterol‐induced β‐adrenergic receptor responses occurred with propranolol. The median provocative dose of albuterol causing a 50% increase in specific airway conductance was 337 and 315 µg (day 1 and day 7, respectively) for placebo, 336 and 322 µg for 4 mg isamoltane, 344 and 389 µg for 10 mg isamoltane, and 667 and 652 µg for propranolol. The provocative dose of albuterol producing a 35% increase in tremor was 464 and 539 µg (day 1 and day 7, respectively) for placebo, 1122 and 1270 µg for 4 mg isamoltane, 1612 and > 1612 µg for 10 mg isamoltane, and > 1612 and > 1612 µg for propranolol. On day 5 of each period an exercise test was performed. Propranolol reduced exercise heart rate by 11% (compared with placebo), 10 mg isamoltane reduced heart rate by 5%, and 4 mg isamoltane reduced heart rate by 1%. In conclusion, low‐dose isamoltane caused measurable systemic effects on both β 2 ‐ and β 1 ‐adrenergic receptors, and the dose‐dependent blockade on β 2 ‐receptors of skeletal muscle was more clear than the attenuation of exercise heart rate. Clinical Pharmacology and Therapeutics (1993) 53 , 675–683; doi: 10.1038/clpt.1993.89