At cholinergic nerve endings and in erythrocytes there is an enzyme that specifically destroys acetylcholine, true cholinesterase or acetylcholinesterase. In various tissues, especially plasma, there are other esterases which are not specific for acetylcholine but which also destroy other esters, e.g. suxamethonium, procaine (and cocaine) and bambuterol (a pro-drug that is hydrolysed to terbutaline). These are called nonspecific or pseudocholinesterases. Chemicals which inactivate these esterases (anticholinesterases) are used in medicine and in agriculture as pesticides. They act by allowing naturally synthesised acetylcholine to accumulate instead of being destroyed. Their effects are almost entirely due to this accumulation in the central nervous system, neuromuscular junction, autonomic ganglia, postganglionic cholinergic nerve endings (which are principally in the parasympathetic nervous system) and in the walls of blood vessels, where acetylcholine has a paracrine role not necessarily associated with nerve endings. Some of these effects oppose each other, e.g. the effect of anticholinesterase on the heart will be the resultant of stimulation at sympathetic ganglia and the opposing effect of stimulation at parasympathetic (vagal) ganglia and at postganglionic nerve endings.

Physostigmine is an alkaloid, obtained from the seeds of the West African Calabar bean (spp. Physostigma), which has long been used both as a weapon and as an ordeal poison.5 It acts for a few hours. Physostigmine is used synergistically with pilocarpine to reduce intraocular pressure. It has been shown to have some efficacy in improving cognitive function in Alzheimer-type dementia.

Neostigmine (t'/2 2 h) is a synthetic reversible anticholinesterase whose actions are more prominent on the neuromuscular junction and the alimentary tract on the cardiovascular system and eye. It is therefore principally used in myasthenia gravis, to stimulate the bowels and bladder after surgery,6 and as an antidote to competitive neuromuscular blocking agents. Neostigmine is effective orally, and by injection (usually s.c.). But higher doses may be used in myasthenia gravis, often combined with atropine to reduce the unwanted muscarinic effects.

Pyridostigmine is similar to neostigmine but has a less powerful action that is slower in onset and slightly longer in duration, and perhaps fewer visceral effects. It is used in myasthenia gravis.

Distigmine is a variant of pyridostigmine (two linked molecules as the name implies).

Edrophonium is structurally related to neostigmine but its action is brief and autonomic effects are minimal except at high doses. The drug is used to diagnose myasthenia gravis and to differentiate a

5 To demonstrate guilt or innocence according to whether the accused died or lived after the judicial dose. The practice had the advantage that the demonstration of guilt provided simultaneous punishment.

6 Ponec R J et al 1999 New England Journal of Medicine 341:

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