Airway smooth muscle cells are innervated (receive nerve supply) by cholinergic nerves. Increased cholinergic nerve activity is associated with irritant stimulation postganglionic cholinergic nerves to result in the release of acetylcholine from postganglionic nerve terminals, thus of sensory nerves in the airways that send impulses to the central nervous system and result in an increase in cholinergic nerve activity to the airways. Electrical impulses (action potentials) emanating from the central nervous system pass down preganglionic cholinergic nerves, traverse a ganglionic synapse (by acetylcholine-dependent neurochemical transmission), and send impulses along postganglionic cholinergic nerves to result in the release of acetycholine from postganglionic nerve terminals. Acetycholine, thus released, acts on muscarinic cholinoceptors that subserve airway smooth muscle contraction and bronchoconstriction (Fig. 3). These actions are prevented by antagonists of muscarinic cholinoceptors or by so-called "atropinelike" drugs. The efficacy of muscarinic cholinoceptor antagonists as bronchodilators is dependent solely on their capacity to reverse airway tone established by acetylcholine or, stated more simply, to terminate bronchoconstriction caused by acetylcholine. Accordingly, the bronchodilator activity of these drugs is dependent on the level of activation of cholinergic nerves, in that the higher the activity of efferent cholinergic nerves, the greater will be the apparent bronchodilator effect of the muscarinic antagonist. This distinguishes muscarinic
antagonists from ^-adrenoceptor agonists, in that the latter are nonspecific in reversing bronchoconstriction induced by a variety of stimuli, including acetylcholine and other bronchoconstrictors, such as inflammatory mediators. Increased activity of cholinergic nerves has been implicated in asthma . However, the efficacy of muscarinic cholinoceptor inhibitors, such as ipratropium bromide, in the treatment of this disease appears to be variable and, in general, inferior to b2-adrenoceptor agonists , a situation that may reflect the variable participation of cholinergic nerves in asthmatic bronchocon-striction. In chronic obstructive pulmonary disease, aerosol coadministration of a muscarinic antagonist with a b2-adrenoceptor agonist induces more profound bronchodilation that either agonist alone  and exploits the rapid onset of action of the b2-adrenoceptor agonist and the long duration of action of the muscarinic antagonist. Studies such as these have fostered the development of combination aerosol therapies, such as ipratropium + albuterol.
In an attempt to reduce the occurrence of side effects associated with absorption into the systemic circulation, quaternary ammonium compounds have been developed as muscarinic cholinoceptor antagonists, for example, ipratropium bromide, glycopyrrolate methylbromide. As a result of their polar nature, these compounds are poorly absorbed across lipid membranes and, therefore, do not easily enter the systemic circulation or the central nervous system (to produce undesirable side effects), but they do induce bronchodilation of long duration [34,35]. The only significant side effect of the quaternary ammonium compounds is dry mouth, an effect perhaps to be expected for a muscarinic cholinoceptor antagonist administered as an aerosol via the mouth.
Three functional subtypes of muscarinic cholinoceptors exist in the airways, designated Mi, M2, and M3. In the airways, agonist activation of Mi and M2 receptors have been proposed to inhibit autonomic ganglionic transmission and acetylcholine release from postganglionic nerves, respectively. M3 receptors are the subtype on airway smooth muscle that mediate contraction of airway smooth muscle . The muscarinic cholinoceptor antagonists used initially as bronchodilators in obstructive airways disease were nonselective for the receptor subtypes. Their ostensible lack of efficacy in treatment of airway obstruction was hypothesized to result from their enhancement of acetylcholine release (by blockage of presynaptic M2 receptors), overwhelming their (postsynaptic M3 receptor) blockade of the contractile actions of released acetylcholine . This encouraged the development of muscarinic antagonists lacking inhibitory activity at the presynaptic M2 receptors, an example of which is tiotropium, which inhibits Mj and M3 cholinoceptors .
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If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.