Rivastigmine Cholinergics

Figure 5. Cartoon of a cholinergic synapse showing major steps in the synthesis of acetylcholine. The two major receptor types, the ionotropic nicotinic receptor and the metabotropic muscarinic receptor, are shown (see also Chapter 1). Presynaptic muscarinic (M2) and nicotinic receptors are also depicted. Drugs which have been widely used to manipulate the cholinergic systems, and which are mentioned in the text, include the muscarinic receptor antagonists scopolamine and atropine and the nicotinic receptor agonist nicotine. Anticholinesterases (discussed elsewhere in this volume) include drugs such as physostigmine, rivastigmine, donepezil, and galanthamine.

Rivastigmine is a pseudo-irreversible inhibitor of both acetyl and butyryl cholinesterases. Thus although the drug initially blocks the enzymes, it is metabolized by them thereby giving the drug a relatively short half-life. The top dose is often necessary to achieve therapeutic efficacy, at which dose the central and peripheral cholinergic side effects become apparent. 

A more recent use of anticholinesterase drugs has been to improve cognitive function in patients with Alzheimer s disease, where both the degree of dementia and amyloid plaque density correlate with the impairment of brain cholinergic function. Donepezil and rivastigmine are licensed in the UK for this indication. Both are orally active and cross the blood-brain barrier readily (see p. 408). 

Alzheimer s disease is associated with a progressive loss of cholinergic neurons in the brain that results in memory disturbances and cognitive dysfunction. One strategy for the treatment of Alzheimer s patients has been the use of acetylcholinesterase (AChE) inhibitors such as rivastigmine to enhance choUnergic activity in the central nervous system,... 

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