Cholinergic antagonist atropine

Cholinergic Antagonists. Atropine, which is a muscarinic antagonist that in some cases also blocks the effects of nicotinic agonists, suppresses REM sleep. The effects of the muscariniclnicotinic agonist carbachol, which facilitates REM sleep, are prevented by systemic administration of atropine. Similarly, scopolamine delays the appearance of REM sleep (35). 

There is also evidence for cholinergic involvement in caffeine analgesia (Ghelardini et al. 1997). The muscarinic antagonists atropine and pirenzepine, and the choline uptake inhibitor hemicholinium-3 prevent caffeine analgesia. In contrast, it was unaffected by an opioid antagonist (naloxone) or a tyrosine hydroxylase inhibitor (o-methyl-p-tyrosine). 

Acetylcholine acts at two different types of cholinergic receptors [see (1) and (2) in Fig. 2.5]. Muscarinic receptors bind ACh as well as other agonists (muscarine, pilocarpine, bethanechol) and antagonists (atropine, scopolamine). There are at least five different types of muscarinic receptors (M1-M5). All have slow response times. They are coupled to G proteins and a variety of second messenger systems. When activated, the final effect can be to open or close channels for K, Ca ", or CL (Bonner, 1989). Nicotinic receptors are less abundant than the muscarinic type in the CNS. They bind ACh as well as agonists such as nicotine or an-... 

Tropane alkaloids are compounds known as muscarinic receptor antagonists. Atropine, its best-known member, and a number of other compounds, block the action of the neurotransmitter acetylcholine on post-ganglionic cholinergic nerves of the parasympathetic nervous system, essentially by blocking its binding to muscarinic cholinergic receptors, whereas they are much less potent at nicotinic receptor sites. 

In F. hepatica and schistosomes, the nicotinic agonist carbachol is a more potent agonist of muscle relaxation/inhibition than is ACh (perhaps because of its insensitivity to esterase). Muscarine is ineffective. Application of the muscarinic antagonist atropine stimulates increased muscle tone, contraction and/or motility and reverses the paralysis induced by carbachol and ACh (9-11, 13, 32). The stimulatory effect of atropine and the ability of eserine (a cholinesterase inhibitor) to relax muscle have fed several investigators to suggest that a tonic release of transmitter from cholinergic cells may be... 

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. ... 

Of the anticholinergics, atropine is the drug most frequently used for the treatment of human poisoning. This muscarinic cholinergic antagonist acts by blocking the overstimulating effects of acetylcholine at the muscarinic... 

Muscarine is a natural alkaloid that is found in a number of wild mushrooms. Despite the fact that muscarine does not have any therapeutic value, it is of interest because of its expressed toxic properties, which made it one of the first systematically studied cholinomimetic substances. This compound was an underlying classification of cholinergic muscarinic receptors. The action of muscarine is similar to that of acetylcholine on peripheral autonomic effector organs, and atropine is an antagonist to it. Unlike acetylcholine, muscarine does not act on nicotinic receptors. 

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.

Frutropium bromide is a derivative of atropine, indicated in the treatment of asthma and bronchitis. It has a cholinergic central effect it is also a muscarinic and histaminic antagonist (Figure 8.50). 

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