Ba 679 BR, a novel long-acting anticholinergic bronchodilator

Area of Science:

• Pulmonary Medicine
• Pharmacology
• Respiratory Therapeutics

Background:

• Anticholinergics are crucial in managing obstructive airway diseases.
• There is a need for inhaled antimuscarinics with improved duration of action.

Purpose of the Study:

• To evaluate a novel antimuscarinic compound, Ba 679 BR, for its potency and duration of action.
• To compare the receptor binding kinetics of Ba 679 BR with ipratropium.

Main Methods:

• Assessed muscarinic antagonist potency in guinea pig tracheal rings.
• Characterized binding affinity (KD values) to human muscarinic receptor subtypes (Hm1, Hm2, Hm3).
• Determined dissociation rates and in vivo duration of action via acetylcholine-induced bronchospasms in dogs.

Main Results:

• Ba 679 BR exhibited high potency and slow dissociation from human muscarinic receptors (e.g., Hm3 half-life of 34.7 hours vs. 0.26 hours for ipratropium).
• In vivo, Ba 679 BR provided a significantly longer duration of protection against bronchospasm than ipratropium.
• Plasma levels in dogs did not correlate with the prolonged pharmacological activity.

Conclusions:

• Ba 679 BR is a novel antimuscarinic bronchodilator with an extended duration of action, likely due to slow dissociation from Hm3 receptors.
• The compound demonstrates kinetic receptor subtype selectivity, dissociating faster from Hm2 than Hm1 and Hm3 receptors.