ANTISYMPATHETIC AGENTS

2011

ANTISYMPATHETIC AGENTS is a grouping of convenience intended to encompass all agents acting by one of the many mechanisms that lead to a reduction in the actions of the sympathetic nervous system, including those of poorly defined mechanism that are known to have this overall action. Antisympathetics are of particular importance in reducing vasomotor tone, and thence blood pressure. There are many of them and they will be grouped by site and mechanism of action. See also ANTIHYPERTENSIVE AGENTS.

Central mechanisms. Some agents may act within the CNS to modify autonomic control of sympathetic tone and blood pressure. Clonidine inhibits release of noradrenaline by an agonist action at the autoinhibitory alpha2-adrenoceptors on sympathetic nerve endings. Methyldopa is thought to work, at least in part, centrally, acting both as an inhibitory false substrate in the biosynthetic pathway, also producing an active metabolite with actions at α2-adrenoceptors. Rauwolfia alkaloids, especially reserpine, which inhibit the monoamine transporters, were at one time used to treat hypertension, but the side-effects are marked.

Biosynthetic pathway inhibitors. In both the central and periphery nervous systems, the biosynthetic pathways for catecholamines, including the sympathetic nervous system transmitter noradrenaline, involve a number of enzymic conversions that may, in principle, be inhibited. There are several inhibitors known that interfere with catecholamine production (e.g. carbidopa or benzerazide) and may therefore act as antisympathetic agents. See DOPA DECARBOXYLASE INHIBITORS; DOPAMINE BETA-HYDROXYLASE INHIBITORS.

Adrenergic neuron blocking drugs. This group of drugs act to prevent the release of noradrenaline from nerves in the central and peripheral divisions of the sympathetic nervous system, and cause an overall fall in blood pressure that is slow to develop, though side-effects limit their use. Examples include bethanidine, bretylium, debrisoquine and guanethidine. See ADRENERGIC NEURON BLOCKING AGENTS.

α-Adrenoceptor antagonists. This is a large group that inhibits certain actions of the sympathetic nervous system by preventing the action of adrenaline and noradrenaline. One use is in lowering blood pressure when it is raised in cardiovascular disease, including in phaeochromocytoma. But a high incidence of side-effects means they are used far less often. See α-ADRENOCEPTOR ANTAGONISTS.

β-Adrenoceptor antagonists. This group is used to lower blood pressure when it is abnormally raised in cardiovascular disease; to correct certain heartbeat irregularities and tachycardias (see ANTIARRHYTHMIC AGENTS); to prevent the pain of angina pectoris during exercise by limiting cardiac stimulation (see ANTIANGINAL AGENTS); to treat myocardial infarction (associated with heart attacks); as prophylaxis to reduce the incidence of migraine attacks (see ANTIMIGRAINE AGENTS); to reduce anxiety, particularly its manifestations such as muscular tremor (see ANXIOLYTIC agents); as a short-term treatment prior to surgical correction of thyrotoxicosis (see ANTITHYROID agents); and as eye-drops to lower raised intraocular pressure in ANTIGLAUCOMA TREATMENT. Side-effects may be minimized by using receptor-subtype-selective β-blockers. Antagonists with similar affinity for (Vadrenoceptor and pVadrenoceptors include nadolol. oxprenolol, propranolol and timolol, whereas acebutolol, atenolol, esmolol and metoprolol show some β1 — adrenoceptor selectivity, and butoxamine is β2-adrenoceptors preferring. See beta-ADRENOCEPTOR ANTAGONISTS.