Pulmonary Disease, Chronic Obstructive Clinical Trial
Official title:
A Study to Optimise the Propranolol Block Model for Assessment of the Pharmacological Activity of Bronchodilators in Healthy Volunteers.
Optimising the propranolol block model
The bronchodilatory effects of inhaled beta2 agonists and anti-muscarinic drugs are the
mainstay of symptomatic treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD).
A new approach is to combine both pharmacological approaches in a single molecule - ie a dual
pharmacophore. It will be necessary to explore the relative contribution of the beta2 agonist
versus anti-muscarinic bronchodilator properties of such a molecule. One way to do that is to
block one of the components. Inhibition of beta2 agonist-mediated bronchodilatation by the
non-selective beta-blocker propranolol is an established experimental method. Therefore this
method may be useful in exploring the pharmacology of a dual pharmacophore.
Published studies have generally looked at the effect of a single dose of propranolol on a
beta2 agonist over a relatively short period of time (a few hours). There is a desire to
develop long acting bronchodilators that require once daily dosing only. Thus any dual
pharmacophore developed is likely to have 24 hour duration of action after a single dose.
Therefore to use this method of beta blockade to inhibit beta2 agonist mediated
bronchodilation, it is necessary to confirm a dosing regimen of propranolol that has
acceptable tolerability and is effective in blocking the effects of a beta2 agonist over 24
hours. That is the main purpose of this study.
It is also important to confirm that the bronchodilator effect of an antimuscarinic is
unaffected by beta blockade. In addition, it is of interest to examine the bronchodilator
effect of a combination of an antimuscarinic and beta2 agonist in healthy volunteers and the
effect of propranolol on the combination.
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