Pharmacological Profile of AZD8871 (LAS191351), a Novel Inhaled Dual M Receptor Antagonist/ -Adrenoceptor Agonist Molecule with Long-Lasting Effects and Favorable Safety Profile.

AZD8871 is a novel muscarinic antagonist and -adrenoceptor agonist in development for chronic obstructive pulmonary disease. This study describes the pharmacological profile of AZD8871 in in vitro and in vivo assays. AZD8871 is potent at the human M receptor (pIC in binding assays: 9.

Deciphering function of the pulmonary arterial sphincters in loggerhead sea turtles ().

To provide new insight into the pathophysiological mechanisms underlying gas emboli (GE) in bycaught loggerhead sea turtles (), we investigated the vasoactive characteristics of the pulmonary and systemic arteries, and the lung parenchyma (LP). Tissues were opportunistically excised from recently dead animals for studies of vasoactive responses to four different neurotransmitters: acetylcholine (ACh; parasympathetic), serotonin (5HT), adrenaline (Adr; sympathetic) and histamine. The significant amount of smooth muscle in the LP contracted in response to ACh, Adr and histamine.

Pharmacological preclinical characterization of LAS190792, a novel inhaled bifunctional muscarinic receptor antagonist /β-adrenoceptor agonist (MABA) molecule.

LAS190792 is a novel muscarinic antagonist and β-adrenoceptor agonist in development for chronic respiratory diseases. This study investigated the pharmacological profile of LAS190792 in comparison to batefenterol, tiotropium, indacaterol and olodaterol. LAS190792 is potent at the human M receptor (pIC: 8.

Evaluation of Mucociliary Clearance by Three Dimension Micro-CT-SPECT in Guinea Pig: Role of Bitter Taste Agonists.

Different image techniques have been used to analyze mucociliary clearance (MCC) in humans, but current small animal MCC analysis using in vivo imaging has not been well defined. Bitter taste receptor (T2R) agonists increase ciliary beat frequency (CBF) and cause bronchodilation but their effects in vivo are not well understood. This work analyzes in vivo nasal and bronchial MCC in guinea pig animals using three dimension (3D) micro-CT-SPECT images and evaluates the effect of T2R agonists.

Vascular effects of sildenafil in patients with pulmonary fibrosis and pulmonary hypertension: an ex vivo/in vitro study.

Sildenafil improves the 6-min walking distance in patients with idiopathic pulmonary fibrosis (IPF) and right-sided ventricular systolic dysfunction.We analysed the previously unexplored role of sildenafil on vasoconstriction and remodelling of pulmonary arteries from patients with IPF and pulmonary hypertension (PH) ex vivo Pulmonary arteries from 18 donors without lung disease, nine IPF, eight PH+IPF and four PH patients were isolated to measure vasodilator and anti-contractile effects of sildenafil in isometric organ bath. Ventilation/perfusion was explored in an animal model of bleomycin lung fibrosis.

Direct effect of cigarette smoke on human pulmonary artery tension.

The effect of chronic cigarette smoke on pulmonary artery (PA) tension has been studied extensively; nevertheless, the direct effect of cigarette smoke is poorly understood. We investigated the direct effect of cigarette smoke extract (CSE) on PA tension in non-smokers, smokers, and COPD patients in vitro. PA samples from 35 patients who underwent lung resection were examined by measuring isometric tension in response to increasing serotonin concentrations.