Anticholinergics acetylcholine

The key has been to avoid using treatments that worsen the disease. In this instance, this means avoiding anticholinergic (acetylcholine-blocking) medications that worsen dementia. As a result, when newer antidepressants such as the SSRIs became available, they quickly replaced the older tricyclic antidepressants because the latter are potent anticholinergics. For the same reason, the low potency anti-psychotics like chlorpromazine (Thorazine) were replaced by the higher potency antipsychotics like haloperidol (Flaldol) and more recently by the atypical antipsychotics. 

Other sleep-inducing benzodiazepines should be avoided. They are more difficult to metabolize and can accumulate in elderly, demented patients. Sedating, low potency antipsychotics should also be avoided. Their strong anticholinergic (acetylcholine-blocking) effects can worsen dementia or cause delirium. 

The Class I agents decrease excitability, slow conduction velocity, inhibit diastoHc depolarization (decrease automaticity), and prolong the refractory period of cardiac tissues (1,2). These agents have anticholinergic effects that may contribute to the observed electrophysiologic effects. Heart rates may become faster by increasing phase 4 diastoHc depolarization in SA and AV nodal cells. This results from inhibition of the action of vagaHy released acetylcholine [S1-84-3] which, allows sympathetically released norepinephrine [51-41-2] (NE) to act on these stmctures (1,2). 

Anticholinergic. A drug that blocks the effects of the neuro-transmitter, acetylcholine. 

Drugp with anticholinergic activity inhibit acetylcholine (a neurohormone produced in excess in Fhrkinson s disease) in the CNS. Dru with anticholinergic activity are generally less effective than levodopa... 

Potential oscillation was measured in the presence of cholinergic agents (acetylcholine chloride, carbamylcholine chloride, carbamyl- d-methylcholine chloride, and acetyl-/6-methylcholine chloride) and anticholinergic agents (tetramethylammonium chloride, tetra-ethylammonium chloride, succinylcholine chloride, hexamethonium chloride, scopolamine hydrobromide, atropine sulfate, homatropine hydrochloride, and tubocurarine chloride)... 

Phenearbamide (60) is a structural analogue of acetylcholine which acts as an anticholinergic agent, possibly by serving as a false agonist. It is made by reacting N,N-diphenylcarbamoyl chloride (59) with 2-mercapto-N,N-diethylethamine. 

Anticholinergic Drugs that block acetylcholine receptors, although the term is used specifically for antagonists at muscarinic acetylcholine receptors (anti-muscarinics), like atropine and scopolamine. 

Agents that decrease acetylcholine activity can alleviate depressive symptoms (i.e, anticholinergic agents). 

Whenever possible, anticholinergic medications should be avoided or kept to a minimum. This is an important consideration because a wide variety of medications, psychiatric and otherwise, possess some acetylcholine-blocking properties. When a patient is using several medications, it is important to review the relative anticholinergic contribution of each medication. Taking one mildly anticholinergic medication may not be a problem, but taking three or four can have additive effects that do become problematic. 

Acetylcholine has been implicated in learning and memory in all mammals, and the gross deficits in memory found in patients suffering from Alzheimer s disease have been ascribed to a defect in central cholinergic transmission. This transmitter has also been implicated in the altered mood states found in mania and depression, while many different classes of psychotropic drugs are known to have potent anticholinergic properties which undoubtedly have adverse consequences for brain function. 

Ipratropium is classified as an anticholinergic because it blocks acetylcholine release. It is indicated in asthma and chronic obstructive pulmonary disease and is available for inhalation. 

Thus, the anticholinergic activity of the alkaloid hyoscyamine is almost entirely confined to the (—)-isomer, and the (+)-isomer is almost devoid of activity. The racemic ( )-form, atropine, has approximately half the activity of the laevorotatory enantiomer. An anticholinergic drug blocks the action of the neurotransmitter acetylcholine, and thus occupies the same binding site as acetylcholine. The major interaction with the receptor involves that part of the molecule that mimics acetylcholine, namely the appropriately positioned ester and amine groups. The chiral centre is adjacent to the ester, and also influences binding to the receptor. 

The Mannich reaction was used for the first synthesis of tropine, the parent alcohol of the tropane alkaloids. One of the natural tropane alkaloids used medicinally is hyoscyamine, sometimes in its racemic form atropine. Hyoscyamine is an anticholinergic, competing with acetylcholine for the muscarinic site of the parasympathetic nervous system, and thus prevendng the passage of nerve impulses. 

The base-catalysed racemization of the alkaloid (-)-hy oscy amine to ( )-hyoscyamine (atropine) is an example of enolate anion participation. Alkaloids are normally extracted from plants by using base, thus liberating the free alkaloid bases from salt combinations. (—)-Hyoscyamine is found in belladonna Atropa belladonna) and stramonium Datura stramonium) and is used medicinally as an anticholinergic. It competes with acetylcholine for the muscarinic site of the parasympathetic nervous system, thus preventing the passage of nerve impulses. However, with careless extraction using too much base the product isolated is atropine, which has only half the biological activity of (—)-hyoscyamine, since the enantiomer (+)-hyoscyamine is essentially inactive. 

Drags that exhibit central anticholinergic properties are used in treating Parkinsonism. It is believed that they do not affect the synthesis, release, or hydrolysis of acetylcholine. Their medicinal efficacy is manifest by the rednction or removal of motor disturbances cansed by damage to the extrapyramidal system. They reduce rigidity, and to a somewhat lesser degree, akinesia, and they have little effect on tremors. 

Pharmacology Ipratropium for oral inhalation is an anticholinergic (parasympatholytic) agent that appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine. The bronchodilation following inhalation is primarily a local, site-specific effect, not a systemic one. 

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