Other cholinergic antagonists

This is the 13-atom connecting chain which connects the two quaternary centres and separates the two centres. 

The cyclic structures at either end of the molecule block the receptor site from acetylcholine. 

These are essential for receptor binding. If one is lost through Hofmann elimination, the binding interaction is too weak and the antagonist leaves the binding site. 

The Hofmann elimination does not occur at acid pH, and so the drug is stable in solution at a pH of 3-4 and can be stored safely in a refrigerator. 

Since the drug only acts very briefly, it has to be added intravenously for as long as it is needed. As soon as surgery is over, the intravenous drip is stopped and antagonism ceases almost instantaneously. 

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The drug most commonly employed as a cholinergic antagonist is atropine, which acts at peripheral and central muscarinic sites. Other cholinergic antagonists which have been investigated include aprophen, benactyzine, scopolamine and trihexyphenidyl. ... 

Nicotinic receptor A primary class of cholinergic receptors, named according to their affinity for nicotine, as well as certain other cholinergic agonists and antagonists. 

Data support the presence and activity of several neurotransmitters in the carotid body ACh, DA, ATP, substance P (SP), adenosine, NO, to name those most frequently studied. Our interest up to the present has focused primarily on the first two. In the cat carotid body ACh functions as an excitatory neurotransmitter. An overwhelming amount of evidence supports an inhibitory role for DA in the cat carotid body, although xmder certain quite limited conditions exogenously administered DA can excite or give a biphasic response. In the rat ATP appears to play as important an excitatory role as ACh (15). Adenosine and NO appear to play important modulatory roles at least. SP can excite the carotid body, but in the cat this effect can be reduced by the use of cholinergic antagonists (14). It is not uncommon for SP to be coreleased with and modulate the effect of ACh in other tissues under cholinergic control (20,21). 

One problem with both these theories is that disruption of noradrenergic transmission by selective adrenoceptor antagonists has little impact on the development of escape deficits. However, such antagonists do prevent the reversal of learned helplessness by antidepressants (reviewed by Stanford 1995). Also, it would be most unlikely that a deficit in only one neurotransmitter system fully accounts for learned helplessness. Indeed, there is plenty of evidence for a role for 5-HT in learned helplessness for instance, this behaviour is reversed by microinjection of 5-HT into the prefrontal cortex (Davis et al. 1999). Finally, it is clear that opioid, GABAergic and cholinergic systems (among others) are all linked with this behavioural deficit and even dihydropyridine antagonists of Ca + channels prevent its development. 

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