chapter  5
18 Pages

Anticholinergics: basic pharmacology

ByM. G. Belvisi, H. J. Patel

The parasympathetic cholinergic nerves play a major role in the control and regulation of airway tone and mucus secretion in man and in animals [1,2]. Acetylcholine (ACh) released from these nerves activates muscarinic receptors on smooth muscle to contract and maintain airway tone, on submucosal glands to stimulate mucus secretion, on blood vessels to cause vasodilation and on cholinergic nerve terminals to inhibit further ACh release. Muscarinic receptor antagonists (anticholinergics) are used as bronchodilators and are central to the management of patients with chronic obstructive pulmonary disease (COPD). Since the 1970s the anticholinergic ipratropium bromide has been widely used for the treatment of patients with regular symptoms. Ipratropium bromide is a nonselective muscarinic antagonist and therefore blocks M2 as well as M1 and M3 receptors, so that the increased ACh release via M2 receptor blockade may overcome the blockade of muscarinic M3 receptors. This has prompted a search for selective muscarinic receptors that block M3 or M1/M3 receptors and for drugs that have a longer duration of action in order to achieve a once-a-day therapy.