ABSTRACT
The muscarinic receptor antagonists interact with the muscarinic receptors, produce no stimulant or agonist effects by themselves, but inhibit the effects of endogenously released Ach or exogenously introduced muscarinic agonists. They therefore inhibit the known physiological responses mediated via muscarinic receptors that have been described in the previous chapter. The principal targets for antagonism are the postjunctional M2 and M3 muscarinic receptors on cardiac and smooth muscle and glandular tissues, which are normally activated by the release of Ach from postganglionic parasympathetic nerve terminals. Additionally, however, the muscarinic receptor located on the cell bodies of postganglionic nerves in autonomic ganglia (M1), the prejunctional receptor (M2) controlling transmitter release from sympathetic and parasympathetic neurones, and the cholinergic sympathetically innervated sweat glands will also be affected. Muscarinic receptors located on non-innervated structures such as certain blood vessels are also antagonized. Finally, muscarinic receptors are distributed throughout the brain and, provided that the antagonist is capable of crossing the blood-brain barrier, the central effects upon mood, behaviour and cognitive powers with therapeutic doses are primarily due to antagonism of muscarinic receptors. In general, the available antagonists have high selectivity for muscarinic compared with nicotinic receptors for Ach; they do not therefore have blocking activity at the somatic nerve-skeletal muscle junction nor at the nicotinic receptors involved in ganglionic transmission, unless doses considerably in excess of muscarinic blocking doses are administered.
