The parasympathetic nervous system, which uses acetylcholine almost exclusively to send its messages, is said to be almost entirely cholinergic. Neuromuscular junctions, preganglionic neurons of the sympathetic nervous system, the basal forebrain, and brain stem complexes are also cholinergic, as are the receptor for the merocrine sweat glands.
In neuroscience and related fields, the term cholinergic is used in these related contexts:
A substance (or ligand) is cholinergic if it is capable of producing, altering, or releasing acetylcholine, or butyrylcholine ("indirect-acting"), or mimicking their behaviours at one or more of the body's acetylcholine receptor ("direct-acting") or butyrylcholine receptor types ("direct-acting"). Such mimics are called parasympathomimetic drugs or cholinomimetic drugs.
A receptor is cholinergic if it uses acetylcholine as its neurotransmitter.[2]
A synapse is cholinergic if it uses acetylcholine as its neurotransmitter.
The hypothesis states that a possible cause of AD is the reduced synthesis of acetylcholine, a neurotransmitter involved in both memory and learning, two important components of AD. Many current drug therapies for AD are centered on the cholinergic hypothesis, although not all have been effective. Studies performed in the 1980s demonstrated significant impairment of cholinergic markers in Alzheimer's patients.[4]
Thus it was proposed that degeneration of cholinergic neurons in the basal forebrain and the associated loss of cholinergic neurotransmission in the cerebral cortex and other areas contributed significantly to the deterioration in cognitive function seen in patients with Alzheimer's disease[5]
Further studies on the cholinergic system and AD demonstrated acetylcholine plays a role in learning and memory. Scopolamine, an anticholinergic drug, was used to block cholinergic activity in young adults and induce memory impairments similar to those present in the elderly. The memory impairments were reversed when treated with physostigmine, a cholinergic agonist. However, reversing memory impairments in AD patients may not be this easy due to permanent changes in brain structure.[6]
When young adults perform memory and attention tasks, brain activation patterns are balanced between the frontal and occipital lobes, creating a balance between bottom-up and top-down processing. Normal cognitive aging may affect long term and working memory, though the cholinergic system and cortical areas maintain performance through functional compensation. Adults with AD presenting with dysfunction of the cholinergic system are not able to compensate for long-term and working memory deficits.[7]
AD is currently treated by increasing acetylcholine concentration by using acetylcholinesterase inhibitors to inhibit acetylcholinesterase from breaking down acetylcholine. Current acetylcholinesterase inhibitors approved in the United States by the FDA to treat Alzheimer's include donepezil, rivastigmine, and galantamine. These drugs work to increase the levels of acetylcholine and subsequently increase the function of neural cells.[8] However, not all treatments based upon the cholinergic hypothesis have been successful in treating the symptoms or slowing the progression of AD.[9] Therefore, a disruption to the cholinergic system has been proposed as a consequence of AD rather than a direct cause.[8]
^Vardanyan, R.S.; Hruby, V.J. (2006). "Cholinomimetics". Synthesis of Essential Drugs. Elsevier. pp. 179–193. doi:10.1016/b978-044452166-8/50013-3. ISBN978-0-444-52166-8. Cholinomimetics or cholinergic drugs are those drugs that cause effects similar to those resulting from introduction of acetylcholine, or simulation of ganglions of the parasympathetic nervous system. These drugs imitate action of endogenously released acetylcholine.
^. Archived from the original on 2010-11-04. Retrieved 2010-10-23.
^Contestabile, A. (August 2011). "The history of the cholinergic hypothesis". Behavioural Brain Research. 221 (2): 334–340. doi:10.1016/j.bbr.2009.12.044. PMID 20060018. S2CID 8089352.
^Bartus RT, Dean RL, Beer B (1982). "The cholinergic hypothesis of geriatric memory dysfunction". Science. 217 (4558): 408–417. Bibcode:1982Sci...217..408B. doi:10.1126/science.7046051. PMID 7046051.
^Craig, L.A.; Hong, N.S.; McDonald, R.J. (May 2011). "Revisiting the cholinergic hypothesis in the development of Alzheimer's disease". Neuroscience & Biobehavioral Reviews. 35 (6): 1397–1409. doi:10.1016/j.neubiorev.2011.03.001. hdl:10133/3693. PMID 21392524. S2CID 37584221.
^Mapstone, M; Dickerson, K; Duffy, CJ (2008). "Distinct mechanisms of impairment in cognitive ageing and Alzheimer's disease". Brain. 131 (6): 1618–1629. doi:10.1093/brain/awn064. PMID 18385184.
^ abTabet, N. (July 2008). "Acetylcholinesterase inhibitors for Alzheimer's disease: anti-inflammatories in acetylcholine clothing". Age Ageing. 35 (4): 336–338. doi:10.1093/ageing/afl027. PMID 16788077.
^Martorana, A; Esposito, Z; Koch, G (August 2010). "Beyond the Cholinergic Hypothesis: Do Current Drugs Work in Alzheimer's Disease?". CNS Neuroscience & Therapeutics. 16 (4): 235–245. doi:10.1111/j.1755-5949.2010.00175.x. PMC6493875. PMID 20560995.
April 13, 2024
cholinergic, agents, compounds, which, mimic, action, acetylcholine, butyrylcholine, general, word, choline, describes, various, quaternary, ammonium, salts, containing, trimethylethanolammonium, cation, found, most, animal, tissues, choline, primary, componen. Cholinergic agents are compounds which mimic the action of acetylcholine and or butyrylcholine 1 In general the word choline describes the various quaternary ammonium salts containing the N N N trimethylethanolammonium cation Found in most animal tissues choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin Choline also prevents fat deposits in the liver and facilitates the movement of fats into cells The N N N trimethylethanolammonium cation with an undefined counteranion X AcetylcholineSee also Cholinomimetic The parasympathetic nervous system which uses acetylcholine almost exclusively to send its messages is said to be almost entirely cholinergic Neuromuscular junctions preganglionic neurons of the sympathetic nervous system the basal forebrain and brain stem complexes are also cholinergic as are the receptor for the merocrine sweat glands In neuroscience and related fields the term cholinergic is used in these related contexts A substance or ligand is cholinergic if it is capable of producing altering or releasing acetylcholine or butyrylcholine indirect acting or mimicking their behaviours at one or more of the body s acetylcholine receptor direct acting or butyrylcholine receptor types direct acting Such mimics are called parasympathomimetic drugs or cholinomimetic drugs A receptor is cholinergic if it uses acetylcholine as its neurotransmitter 2 A synapse is cholinergic if it uses acetylcholine as its neurotransmitter Contents 1 Cholinergic drug 1 1 Structure activity relationship for cholinergic drugs 2 Cholinergic hypothesis of Alzheimer s disease 3 See also 4 ReferencesCholinergic drug editMain article Parasympathomimetic drug Structure activity relationship for cholinergic drugs edit A molecule must possess a nitrogen atom capable of bearing a positive charge preferably a quaternary ammonium salt For maximum potency the size of the alkyl groups substituted on the nitrogen should not exceed the size of a methyl group The molecule should have an oxygen atom preferably an ester like oxygen capable of participating in a hydrogen bond A two carbon unit should occur between the oxygen atom and the nitrogen atom There must be two methyl groups on the nitrogen A larger third alkyl group is tolerated but more than one large alkyl groups leads to loss of activity The overall size of the molecule cannot be altered much Bigger molecules have poorer activity 3 Cholinergic hypothesis of Alzheimer s disease editMain article Alzheimer s disease See also Cholinesterase inhibitor The hypothesis states that a possible cause of AD is the reduced synthesis of acetylcholine a neurotransmitter involved in both memory and learning two important components of AD Many current drug therapies for AD are centered on the cholinergic hypothesis although not all have been effective Studies performed in the 1980s demonstrated significant impairment of cholinergic markers in Alzheimer s patients 4 Thus it was proposed that degeneration of cholinergic neurons in the basal forebrain and the associated loss of cholinergic neurotransmission in the cerebral cortex and other areas contributed significantly to the deterioration in cognitive function seen in patients with Alzheimer s disease 5 Further studies on the cholinergic system and AD demonstrated acetylcholine plays a role in learning and memory Scopolamine an anticholinergic drug was used to block cholinergic activity in young adults and induce memory impairments similar to those present in the elderly The memory impairments were reversed when treated with physostigmine a cholinergic agonist However reversing memory impairments in AD patients may not be this easy due to permanent changes in brain structure 6 When young adults perform memory and attention tasks brain activation patterns are balanced between the frontal and occipital lobes creating a balance between bottom up and top down processing Normal cognitive aging may affect long term and working memory though the cholinergic system and cortical areas maintain performance through functional compensation Adults with AD presenting with dysfunction of the cholinergic system are not able to compensate for long term and working memory deficits 7 AD is currently treated by increasing acetylcholine concentration by using acetylcholinesterase inhibitors to inhibit acetylcholinesterase from breaking down acetylcholine Current acetylcholinesterase inhibitors approved in the United States by the FDA to treat Alzheimer s include donepezil rivastigmine and galantamine These drugs work to increase the levels of acetylcholine and subsequently increase the function of neural cells 8 However not all treatments based upon the cholinergic hypothesis have been successful in treating the symptoms or slowing the progression of AD 9 Therefore a disruption to the cholinergic system has been proposed as a consequence of AD rather than a direct cause 8 See also editAdrenergic Anticholinergic Dopaminergic GABAergic Glutamatergic moly herb Nootropic Racetam Serotonergic Nicotinic acetylcholine receptorReferences edit Vardanyan R S Hruby V J 2006 Cholinomimetics Synthesis of Essential Drugs Elsevier pp 179 193 doi 10 1016 b978 044452166 8 50013 3 ISBN 978 0 444 52166 8 Cholinomimetics or cholinergic drugs are those drugs that cause effects similar to those resulting from introduction of acetylcholine or simulation of ganglions of the parasympathetic nervous system These drugs imitate action of endogenously released acetylcholine Dorlands Medical Dictionary cholinergic receptors permanent dead link Medicinal Chemistry of Adrenergics and Cholinergics Archived from the original on 2010 11 04 Retrieved 2010 10 23 Contestabile A August 2011 The history of the cholinergic hypothesis Behavioural Brain Research 221 2 334 340 doi 10 1016 j bbr 2009 12 044 PMID 20060018 S2CID 8089352 Bartus RT Dean RL Beer B 1982 The cholinergic hypothesis of geriatric memory dysfunction Science 217 4558 408 417 Bibcode 1982Sci 217 408B doi 10 1126 science 7046051 PMID 7046051 Craig L A Hong N S McDonald R J May 2011 Revisiting the cholinergic hypothesis in the development of Alzheimer s disease Neuroscience amp Biobehavioral Reviews 35 6 1397 1409 doi 10 1016 j neubiorev 2011 03 001 hdl 10133 3693 PMID 21392524 S2CID 37584221 Mapstone M Dickerson K Duffy CJ 2008 Distinct mechanisms of impairment in cognitive ageing and Alzheimer s disease Brain 131 6 1618 1629 doi 10 1093 brain awn064 PMID 18385184 a b Tabet N July 2008 Acetylcholinesterase inhibitors for Alzheimer s disease anti inflammatories in acetylcholine clothing Age Ageing 35 4 336 338 doi 10 1093 ageing afl027 PMID 16788077 Martorana A Esposito Z Koch G August 2010 Beyond the Cholinergic Hypothesis Do Current Drugs Work in Alzheimer s Disease CNS Neuroscience amp Therapeutics 16 4 235 245 doi 10 1111 j 1755 5949 2010 00175 x PMC 6493875 PMID 20560995 Retrieved from https en wikipedia org w index php title Cholinergic amp oldid 1191085584, wikipedia, wiki, book, books, library,
