Nicotinic agonists brain

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The a4p2 nAChR is the predominant heteromeric receptor in the brain, binds nicotine and other nicotinic agonists, e.g. cytisine and epibatidine. As a principal nicotinic AChR is more ubiquitous and is predominant in cortex, striatum, superior colliculus, lateral geniculate nucleus and cerebellum. When activated it facilitates excitatory inputs and is present very early in the developing brain in various brain regions. 

This chapter will briefly examine potential clinical applications of nicotine and/or nicotinic agonists in a variety of CNS disorders with particular emphasis on structural brain disease. For further details, the reader is referred to a more comprehensive review (Newhouse and Kelton, 1999). Clinical areas covered include cognitive disorders, move-... 

It is possible that use of agonists rather than antagonists as probes will be useful. Racemic, tritium-labeled nicotine itself was shown to bind stereospecifically to rat brain tissue with high affinity, which binding could be inhibited by other nicotinic agonists, but not antagonists. 

In contrast to the nicotinic antagonists and indeed both nicotinic and muscarinic agonists, there are a number of muscarinic antagonists, like atropine, hyoscine (scopolamine) and benztropine, that readily cross the blood-brain barrier to produce central effects. Somewhat surprisingly, atropine is a central stimulant while hyoscine is sedative, as least in reasonable doses. This would be the expected effect of a drug that is blocking the excitatory effects of ACh on neurons but since the stimulant action of atropine can be reversed by an anticholinesterase it is still presumed to involve ACh in some way. Generally these compounds are effective in the control of motion but not other forms of sickness (especially hyoscine), tend to impair memory (Chapter 18) and reduce some of the symptoms of Parkinsonism (Chapter 15). 

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