Nicotinic action of acetylcholine

Bethanechol is a quaternary ammonium compound that shares both the muscarinic and nicotinic actions of acetylcholine but it is much more slowly deactivated. It has been used to treat clomipramine-induced orgasmic dysfunction (1). 

Carbachol is a quaternary ammonium compound that shares both the muscarinic and nicotinic actions of acetylcholine but is much more slowly deactivated. Carbachol has been used topically in ophthalmology and systemically (subcutaneously, for example in doses of 2 mg/day) for urinary retention. Severe cholinergic effects can result. In one instance they primarily involved the gastrointestinal tract and the patient died of esophageal rupture (1). In other cases patients have experienced extreme bradycardia with hypotension, requiring treatment with intravenous atropine. As carbachol is not destroyed by cholinesterase, a cumulative effect is possible in patients who receive regular doses at short intervals in one case, hypotension only developed on the third treatment day (2). 

It possesses both muscarinic and nicotinic actions of acetylcholine. It is used for its miotic actions in the treatment of primary glaucoma. It is employed invariably in urinary retention, peripheral vascular disease and intestinal paresis. 

In human medicine, carbachol (carbamoylcholine chloride) 2.11), which is isosteric with acetylcholine 2.7), is used to block acetylcholinesterase and is slowly hydrolysed by it. It exhibits both the muscarinic and nicotinic actions of acetylcholine in a more prolonged and intense form. Other examples used in... 

The optimal position for an oxygen atom in the side-chain. The ether ( 3-59) has approximately i to lo per cent of the activity of acetylcholine, and is more active at muscarinic than at nicotinic sites. This activity is diminished if the oxygen atom is moved from the 3- to the 2- or 4-position. The ketone (13.61) has little muscarinic (but from 0.2 to too per cent of the nicotinic) action of acetylcholine on various test preparations. If the carbonyl-group is moved from the 4- to the 3- or 2-position, the action is diminished (Ing, Kordik, and Williams, 1952). Thus both the ethereal and carbonyl oxygen atoms have maximal activity in the positions where they occur in acetylcholine (13.44). 

Egan, T. M. North, R. A. (1986). Actions of acetylcholine and nicotine on rat locus coeruleus neurons in vitro. Neuroscience 19, 565-71. 

Before proceeding further we may note that many pharmacologists have found it convenient to describe the action at a synapse or neuromuscular junction as nicotine-like or muscarinelike as the case may be (see figs. 3 and 6). Thus the effect of nicotine resembles the action of acetylcholine at the junction... 

Things turn out to be a bit more complex than I have suggested thus far. Acetylcholine is also known to cause contraction of skeletal muscle and to slow the rate of heartbeat. However, muscarine does neither of these things nor are these actions of acetylcholine blocked by atropine. Another plant-derived molecule, nicotine from tobacco, proved to be an acetylchohne agonist at skeletal muscle and heart. 

So, parasympathetic nerves use acetylcholine as a neurotransmitter and cholinomimetic drugs mimic the action of acetylcholine at its receptors. Muscarinic receptor subtypes are found on neuroeffector junctions. Nicotinic receptor subtypes are found on ganglionic synapses. Chohnomimetics can be classified as ... 

These agents inhibit the muscarinic actions of acetylcholine at postganglionic parasympathetic neuroeffector sites including smooth muscle, secretory glands, and CNS sites. Large doses may block nicotinic receptors at the autonomic ganglia and at the neuromuscular junction. 

The administration of acetylcholine mimics the stimulatory effect of nicotine, the alkaloid from the tobacco plant, on autonomic ganglia and the adrenal medulla. It has become common practice to refer to the effects of acetylcholine on visceral effectors as the muscarinic action of acetylcholine and to its effects on the... 

The action of acetylcholine at the skeletal muscle motor end plate resembles that produced by nicotine. Thus, the choUnoreceptor on skeletal muscle is a nicotinic receptor. Based on antagonist selectivity, however, the autonomic and somatic nicotinic receptors are not pharmacologically identical (see Chapter 14). 

The actions of acetylcholine released from autonomic and somatic motor nerves are terminated by enzymatic hydrolysis of the molecule. Hydrolysis is accomplished by the action of acetylcholinesterase, which is present in high concentrations in cholinergic synapses. The indirect-acting cholinomimetics have their primary effect at the active site of this enzyme, although some also have direct actions at nicotinic receptors. The chief differences between members of the group are chemical and pharmacokinetic—their pharmacodynamic properties are almost identical. 

The toxic effects can be divided into three types as the accumulation of acetylcholine leads to symptoms that mimic the muscarinic, nicotinic, and CNS actions of acetylcholine. Muscarinic receptors for acetylcholine are found in smooth muscles, the heart, and exocrine glands. Therefore, the signs and symptoms are tightness of the chest, wheezing due to bronchoconstriction, bradycardia, and constriction of the pupils (miosis). Salivation, lacrimation, and sweating are all increased, and peristalsis is increased, leading to nausea, vomiting, and diarrhea. 

Nicotinic signs and symptoms result from the accumulation of acetylcholine at motor nerve endings in skeletal muscle and autonomic ganglia. Thus, there is fatigue, involuntary twitching, and muscular weakness, which may affect the muscles of respiration. Hypertension and hyperglycemia may also reflect the action of acetylcholine at sympathetic ganglia. 

Acetylcholine receptors are classified as either muscarinic cholinergic receptors or nicotinic cholinergic receptors. The alkaloid muscarine mimics the effects produced by stimulation of the parasympathetic system. These effects are postganglionic and are exerted on exocrine glands, cardiac muscle, and smooth muscle. The alkaloid nicotine mimics the actions of acetylcholine, which include stimulation of all autonomic ganglia, stimulation of the adrenal medulla, and contraction of skeletal muscle. 

The tobacco compound nicotine has been used as an insecticide for over 200 years. It is especially effective against sucking insects, such as aphids, and has excellent contact activity. Related compounds are neonicotinoids (e.g., imidacloprid), which have similar insecticidal activity, but are less toxic to mammals. Nicotine and imidacloprid mimic the action of acetylcholine, which is the major excitatory neurotransmitter in an insect s central nervous system. The action of acetylcholine is stopped by the enzyme acetylcholinesterase, which rapidly breaks down acetylcholine. Nicotine and imidacloprid are also neuroexcitatory, but do so persistendy, since they are not affected by acetylcholinesterase. Overstimulation of the nervous system often leads to convulsions, paralysis, and death. 

Two families of cholinoceptors, designated muscarinic and nicotinic receptors, can be distinguished from each other on the basis of their different affinities for agents that mimic the action of acetylcholine (cholinomimetic agents). 

Modulates nicotinic receptors, which enhances actions of acetylcholine... 

Acetylcholine is the endogenous neurotransmitter at cholinergic synapses and neuroeffector junctions in the central and peripheral nervous systems. The actions of acetylcholine are mediated through nicotinic and muscarinic cholinergic receptors, which transduce signals via distinct mechanisms. 

Only a few physiological studies on the actions of acetylcholine in the cerebellar cortex have been reported and the results of these studies were often contradictory lonto-phoretic application of acetylcholine has been observed to mildly excite Purkinje cells via a muscarinic (Crawford et al., 1966) or a nicotic (McCance and Phillis, 1968) mechanism, or to inhibit them via a mixed muscarinic and nicotinic mechanism. For interneurons no effect of acetylcholine was found by Crawford et al. (1966), whereas De la Garza et al. (1987) found a strong nicotinic excitatory effect. Crepel and Dhanjal... 

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