Effect of Ba 679 BR, a novel long-acting anticholinergic agent, on cholinergic neurotransmission in guinea pig and human airways
| Autor: | Samad Tadjkarimi, Magdi H. Yacoub, Hemma Patel, J. K. Ward, Maria G. Belvisi, Peter J. Barnes, T. Takahashi |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine medicine.medical_specialty Time Factors Guinea Pigs Scopolamine Derivatives Bronchi In Vitro Techniques Ipratropium bromide Critical Care and Intensive Care Medicine Synaptic Transmission Cholinergic Antagonists Guinea pig Internal medicine Muscarinic acetylcholine receptor medicine Animals Humans Tiotropium Bromide Antimuscarinic Agent business.industry Muscle Smooth Muscarinic acetylcholine receptor M2 Receptors Muscarinic Acetylcholine Bronchodilator Agents Trachea Atropine Endocrinology Cholinergic Fibers Cholinergic business Muscle Contraction medicine.drug |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 150:1640-1645 |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/ajrccm.150.6.7952627 |
| Popis: | We investigated the effect of Ba 679 BR, a novel long-acting antimuscarinic agent, on cholinergic neural responses in guinea pig and human airways. Ba 679 BR, atropine, and ipratropium bromide inhibited electrical field stimulation (EFS)-induced contraction with IC50 values of 0.17, 0.74, and 0.58 nM, respectively, in guinea pig trachea. Ba 679 BR had a slower onset and longer duration of action than atropine or ipratropium bromide (the times required to attain 50% of the maximum response were 34.8, 3.8, and 7.6 min, respectively, and the times required for 50% recovery of the response were 540, 31.6, and 81.2 min, respectively). Ba 679 BR, as well as atropine and ipratropium bromide, facilitated evoked [3H]acetylcholine release (an inhibitory effect on prejunctional muscarinic M2 receptors). The facilitation of acetylcholine release by Ba 679 BR was lost 2 h after washout, however, when there was still complete blockade of cholinergic contractile responses evoked by EFS (an effect on airway smooth muscle M3 receptors), confirming binding studies that suggest that Ba 679 BR shows "kinetic receptor subtype selectivity" for M3 over M2 receptors. The high potency, slow onset, and long duration of action of Ba 679 BR were also observed in human bronchi, suggesting that Ba 679 BR may be a useful drug to provide convenient therapy for patients with obstructive airway disease. |
| Databáze: | OpenAIRE |
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