Cholinergic

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The N,N,N-trimethylethanolammonium cation, with an undefined counteranion, X

In general, the word choline refers to 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. It prevents fat deposits in the liver and facilitates the movement of fats into the cells. The richest sources of choline are liver, kidney, brain, wheat germ, brewer's yeast, and egg yolk. Neurologically, cholinergic is the abbreviated term referring to acetylcholine.[1] 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. In addition, the receptor for the merocrine sweat glands are also cholinergic, since acetylcholine is released from post-ganglionic sympathetic neurons.

In neuroscience and related fields, the term cholinergic is used in the following related contexts:

  • A substance (or ligand) is cholinergic if it is capable of producing, altering, or releasing acetylcholine ("indirect-acting") or mimicking its behaviour at one or more of the body's acetylcholine receptor types ("direct-acting").
  • A receptor is cholinergic if it uses acetylcholine as its neurotransmitter.[2]
  • A synapse is cholinergic if it uses acetylcholine as its neurotransmitter.

Cholinergic drug[edit]

Structure activity relationship for cholinergic drugs[3][edit]

1. Molecule must possess a nitrogen atom capable of bearing a positive charge, preferably a quaternary ammonium salt.

2. For maximum potency, the size of the alkyl groups substituted on the Nitrogen should not exceed the size of a methyl group.

3. The molecule should have an oxygen atom, preferably an ester-like oxygen capable of participating in a hydrogen bond.

4. There should be a two-carbon unit between the oxygen atom and the nitrogen atom.

Cholinergic hypothesis of Alzheimer's disease[edit]

Main article: Alzheimer's disease

As researchers began to focus on neurotransmitter imbalances as a cause of AD, the cholinergic hypothesis was proposed. The hypothesis states that a possible cause of Alzheimer's Disease is the reduced synthesis of acetylcholine, a neurotransmitter which is involved in both memory and learning, two important components of AD. Many current drug therapies for AD are centered around 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]

Further studies on the cholinergic system and AD demonstrated that 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, it may not be this easy to reverse memory impairments in AD patients due to permanent changes in brain structure.[5]

When young adults perform memory and attention tasks, brain activation patterns are balanced between the frontal lobe and occipital lobe, 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 will maintain performance through functional compensation. Adults with AD presenting with dysfunction of the cholinergic system will not be able to compensate for long term and working memory deficits.[6]

AD is currently treated by increasing acetylcholine concentration by using acetylcholinesterase inhibitors to inhibit acetylcholinesterase from breaking down acetylcholine. Current acetylcholinesterase inhibitors approved by the FDA to treat Alzheimer’s include Aricept, Exelon and Reminyl. These drugs work to increase the levels of acetylcholine and subsequently increase the function of neural cells.[7] However, not all treatments based upon the cholinergic hypothesis have been successful in treating the symptoms or slowing the progression of AD.[8] Therefore, it has been proposed that a disruption to the cholinergic system is a consequence of AD rather than a direct cause of AD.[7]

See also[edit]

References[edit]

  1. ^ "Definition: cholinergic from Online Medical Dictionary". 
  2. ^ "Dorlands Medical Dictionary:cholinergic receptors". 
  3. ^ Medicinal Chemistry of Adrenergics and Cholinergics
  4. ^ Contestabile, A. (August 2011). "The history of the cholinergic hypothesis". Behavioral Brain Research 221 (2): 334–340. doi:10.1016/j.bbr.2009.12.044. 
  5. ^ Craig, L.A., Hong, N.S., McDonald, R.J. (May 2011). "Revisiting the cholinergic hypothesis in the development of Alzheimer's disease". Neuroscience & Behavioral Reviews 35 (6): 1397–1409. doi:10.1016/j.neubiorev.2011.03.001. 
  6. ^ Mapstone, M, Dickerson, K, Duffy, C.J. (2008). "Distinct mechanisms of impairment in cognitive ageing and Alzheimer’s disease.". Brain 131: 1618–1629. doi:10.1093/brain/awn064. 
  7. ^ 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. 
  8. ^ 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.