Autonomic nervous system pharmacology

Abstract

The autonomic nervous system (ANS) comprises the sympathetic and parasympathetic nervous systems. Ganglionic synaptic transmission in the ANS is mediated by the release of acetylcholine from the preganglionic neurone. Both muscarinic and nicotinic receptors are involved in mediation of the postganglionic response, as are inhibitory dopaminergic interneurones. In general, sympathetic postganglionic neurones are noradrenergic, and parasympathetic postganglionic neurones are muscarinic (cholinergic). The two systems tend to have opposite actions. Deliberate pharmacological manipulation of the ANS is therefore aimed at sites where physiological or anatomical differences exist between the two systems. Cholinergic system The important structural features of the neurotransmitter acetylcholine are the strongly positive quaternary amine in the choline part of the molecule and the ester component with its partial negative charge. Choline receptor antagonists have either a tertiary or a quaternary amine (or both). Acetylcholine receptors are classified as either muscarinic or nicotinic. Nicotinic receptors are widespread in the body, and are found in both sympathetic and parasympathetic nervous systems. Drug actions at the nicotinic receptors of the neuromuscular junction, which is not part of the ANS, are covered in Section 3, Chapter 8. Muscarinic receptors The muscarinic receptors are G-protein-coupled receptors. Five subtypes have been identified (M 1–5 ), but the most important ones are M 1 , M 2 and M 3 , which are all antagonised by atropine. M 1 receptors are found in the central nervous system (CNS), autonomic ganglia and gastric parietal cells, M 2 receptors are found in the heart and at presynaptic sites, and M 3 receptors are found in smooth muscle, vascular endothelium (causing vasodilatation) and in exocrine glands.