Cholinergic agents are compounds which mimic the action of

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

and/or butyrylcholine. In general, the word " choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium

cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

. Found in most animal tissues, choline is a primary component of the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

and functions with

inositol Inositol, or more precisely ''myo''-inositol, is a carbocyclic sugar that is abundant in the brain and other mammalian tissues; it mediates cell signal transduction in response to a variety of hormones, neurotransmitters, and growth factors and ...

as a basic constituent of

lecithin Lecithin (, from the Greek ''lekithos'' "yolk") is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues which are amphiphilic – they attract both water and fatty substances (and so ar ...

. Choline also prevents fat deposits in the liver and facilitates the movement of fats into cells. The

parasympathetic nervous system The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of ...

, 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 sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of th ...

, 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 In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...

) is cholinergic if it is capable of producing, altering, or releasing

, 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 Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

is cholinergic if it uses acetylcholine as its neurotransmitter. * A

synapse In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...

is cholinergic if it uses acetylcholine as its neurotransmitter.

Cholinergic drug

Structure activity relationship for cholinergic drugs

# 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

Cholinergic hypothesis of Alzheimer's disease

The hypothesis states that a possible cause of AD is the reduced synthesis of

, 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. 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 Further studies on the cholinergic system and AD demonstrated acetylcholine plays a role in learning and memory.

Scopolamine Scopolamine, also known as hyoscine, or Devil's Breath, is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is formally used as a medication for treating motion sickness and postoperative nausea and vomiting ...

, 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. When young adults perform memory and attention tasks, brain activation patterns are balanced between the

frontal Front may refer to: Arts, entertainment, and media Films * ''The Front'' (1943 film), a 1943 Soviet drama film * ''The Front'', 1976 film Music *The Front (band), an American rock band signed to Columbia Records and active in the 1980s and ea ...

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. AD is currently treated by increasing acetylcholine concentration by using acetylcholinesterase inhibitors to inhibit

acetylcholinesterase Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme Enzymes () are proteins that a ...

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. However, not all treatments based upon the cholinergic hypothesis have been successful in treating the symptoms or slowing the progression of AD. Therefore, a disruption to the cholinergic system has been proposed as a consequence of AD rather than a direct cause.

References

{{Acetylcholine metabolism and transport modulators Parasympathetic nervous system Neurochemistry Sympathomimetics

Cholinergic drug

Structure activity relationship for cholinergic drugs

Cholinergic hypothesis of Alzheimer's disease

See also

References