Muscarinic action

General types of physiological functions attributed to quaternary ammonium compounds are curare action, muscarinic—nicotinic action, and ganglia blocking action. The active substance of curare is a quaternary that can produce muscular paralysis without affecting the central nervous system or the heart. Muscarinic action is the stimulation of smooth-muscle tissue. Nicotinic action is primary transient stimulation and secondary persistent depression of sympathetic and parasympathetic ganglia. 

In view of the preponderance of muscarinic receptors in the CNS and the conceived need to augment the muscarinic actions of ACh in the treatment of Alzheimer s disease, much attention has been given recently to the synthesis of agonists that penetrate the blood-brain barrier, especially those that act specifically on M] receptors. 

The answer is g. (Hardman, p 870. Katzung, pp 230-231) Quini-dine causes prolongation of the QT interval at therapeutic doses, possibly because of its anti muscarinic actions In some patients, this is associated with recurrent lightheaded ness and fainting (known as qmmdine syncope). The symptoms result from torsades de pointes. They typically terminate but may become fatal by degeneration into ventricular fibrillation. 

Iwamoto FT. (1989). Antinociception after nicotine administration into the mesopontine tegmentum of rats Evidence for muscarinic actions. J Pharmacol Exp Ther. 251 412-21. 

Nicotinic signs of intoxication include muscle weakness, tremor and fasciculations, and involuntary twitching. Muscle weakness that affects the respiratory muscles may contribute to dyspnea and cyanosis. Tachycardia may result from stimulation of sympathetic ganglia in cardiac tissue and may mask the bradycardia due to the muscarinic action on the heart. Nicotinic action at the sympathetic ganglion may also result in pallor, high blood pressure, and hyperglycemia. 

Methscopolamine inhibits the muscarinic action of acetylcholine on postganlionic para sympathetic effector regions. It is used for treating stomach ulcers. Synonyms of this drag are pamine and scoline. 

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. 

Muscarinic receptor activation of cortical pyramidal cells occurs with a latency of around 250 msec (Taylor 8c Brown, 1999). There is also an approximate 500 msec time lag between the occurrence of a stimulus and consciousness of that stimulus (Libet et ah, 1991). Hence the typical delay associated with muscarinic action (and that of other metabotropic receptors) coincides with the time lag for stimuli reaching consciousness. Thus, cholinergic affer-ents to the cerebral cortex may contribute to 40 Hz activity, as well as to larger envelopes of activity (or inactivity) lasting 250-500 msec. 

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... 

Mechanism of Action Competitive inhibitors of the muscarinic actions of acetylcholine, acting at receptors located in exocrine glands, smooth and cardiac muscle, and intramural neurons. Composed of 3 main constituents atropine, scopolamine, and hyoscyamine. Scopolamine exerts greater effects on the CNS, eye, and secretory glands than the constituents atropine and hyoscyamine. Atropine exerts more activity on the heart, intestine, and bronchial muscle and exhibits a more prolonged duration of action compared to scopolamine. Hyoscyamine exerts similar actions to atropine but has more potent central and peripheral nervous system effects. TherapeuticEffect Peripheral anticholinergic and antispasmodic action, mild sedation. Pharmacokinetics None known... 

It soon became evident that no available antidotes could block the pharmacologic activity of these chemicals, alleviate the signs and symptoms of toxicity, or restore normal bodily functions after exposure. Atropine readily antagonized the muscarinic actions, including those in the central nervous system (CNS), but elicited no reversal of the nicotinic effects. Better forms of therapy were sought, particularly to alleviate the nicotinic effects of anticholinesterase agents. 

Acetylcholine (4.1) has, of course, both nicotinic and muscarinic action. Because it is very rapidly hydrolyzed by AChE and even by aqueous solution, it is not used therapeutically. 

It is resistant to hydrolysis by both true and pseudocholinesterase and has mainly muscarinic actions. It has been used in postoperative and postpartum nonobstructive urinary retention and gastroesophageal reflux. 

Choline Ester Susceptibility to Cholinesterase Muscarinic Action Nicotinic Action... 

Tachjtphylaxis occurs and a phase II block develops readily (2). In high doses, muscarinic actions can be seen and histamine release can occur. 

Beckett and coworkers (147) reported the approximate equivalence of muscarinic action shown by enantiomers of 4,5-dehydromusca-rone (104). 

The muscarinic actions of acetylcholine can be either stimulatory or inhibitory. Acetylcholine stimulates secretion and contraction of the gut, but it inhibits the contraction of the heart and relaxes the smooth muscle of blood vessels. Acetylcholine can inhibit adenylate cyclase and activate guanylate cyclase. In the cortical neurones, muscarinic agents cause a slow depolarization mediated by closing potas-... 

The actual signs and symptoms observed depend on the balance of muscarinic and nicotinic receptor activation. While miosis (muscarinic action) is most common, it may not always be present, and indeed mydriasis (nicotinic action) may occur. Likewise tachycardia (nicotinic effect) may be present rather than bradycardia (muscarinic action). Death most commonly results from respiratory failure, a consequence of nicotinic receptor-mediated muscle paralysis, combined with muscarmic-facilitated bronchorrhea, bronchoconstriction, and CNS depression. 

The physiological effects of LSD are related to its sympathomimetic actions and include mydriasis (most frequent and consistent), tachycardia, increased body temperature, diaphoresis, and hypertension at higher doses, parasympathomimetic actions may be observed (e.g., salivation, lacrimation, nausea, and vomiting [muscarinic actions]). Neuromuscular effects may include paresthesia, muscle twitches, and incoordination (nicotinic actions)... 

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