Acetylcholine (Neurotransmitter)

IUPAC Name: 2-Acetoxy-N,N,N-trimethylethanaminium

Acetylcholine, an ester of choline and acetic acid that serves as a transmitter substance of nerve impulses within the central and peripheral nervous systems. Acetylcholine is the chief neurotransmitter of the parasympathetic nervous system, the part of the autonomic nervous system (a branch of the peripheral nervous system) that contracts smooth muscles, dilates blood vessels, increases bodily secretions, and slows heart rate. Acetylcholine can stimulate a response or block a response and thus can have excitatory or inhibitory effects.

Acetylcholine is stored in vesicles at the ends of cholinergic (acetylcholine-producing) neurons. In the peripheral nervous system, when a nerve impulse arrives at the terminal of a motor neuron, acetylcholine is released into the neuromuscular junction. There it combines with a receptor molecule in the postsynaptic membrane (or end-plate membrane) of a muscle fibre. This bonding changes the permeability of the membrane, causing channels to open that allow positively charged sodium ions to flow into the muscle cell (see end-plate potential). If successive nerve impulses accumulate at a sufficiently high frequency, sodium channels along the end-plate membrane become fully activated, resulting in muscle cell contraction.

The nicotinic acetylcholine receptor is an example of a ligand-gated ion channel. It is composed of five subunits arranged symmetrically around a central conducting pore. Upon binding acetylcholine, the channel opens and allows diffusion of sodium (Na+) and potassium (K+) ions through the conducting pore.

Within the autonomic nervous system, acetylcholine behaves in a similar manner, being discharged from the terminal of one neuron and binding to receptors on the postsynaptic membrane of other cells. Its activities within the autonomic nervous system affect a number of body systems, including the cardiovascular system, where it acts as a vasodilator, decreases heart rate, and decreases heart muscle contraction. In the gastrointestinal system, it acts to increase peristalsis in the stomach and the amplitude of digestive contractions. In the urinary tract, its activity decreases the capacity of the bladder and increases voluntary voiding pressure. It also affects the respiratory system and stimulates secretion by all glands that receive parasympathetic nerve impulses. In the central nervous system, acetylcholine appears to have multiple roles. It is known to play an important role in memory and learning and is in abnormally short supply in the brains of persons with Alzheimer disease.

Acetylcholine is rapidly destroyed by the enzyme acetylcholinesterase and thus is effective only briefly. Inhibitors of the enzyme (drugs known as anticholinesterases) prolong the lifetime of acetylcholine. Such agents include physostigmine and neostigmine, which are used to help augment muscle contraction in certain gastrointestinal conditions and in myasthenia gravis. Other acetylcholinesterases have been used in the treatment of Alzheimer disease.

Naturally occurring acetylcholine was first isolated in 1913 by English chemist Arthur James Ewins, at the urging of his colleague, physiologist Sir Henry Dale, who in 1914 described the chemical’s actions. The functional significance of acetylcholine was first established about 1921 by German physiologist Otto Loewi. Loewi demonstrated that acetylcholine is liberated when the vagus nerve is stimulated, causing slowing of the heartbeat. Subsequently he and others showed that the chemical is also liberated as a transmitter at the motor end plate of striated (voluntary) muscles of vertebrates. It subsequently was identified as a transmitter at many neural synapses and in many invertebrate systems as well. Owing to Dale’s and Loewi’s work, acetylcholine became the first neurotransmitter to be identified and characterized. For their work, the two men shared the 1936 Nobel Prize for Physiology or Medicine.

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What happens when acetylcholine increases?
Excessive accumulation of acetylcholine (ACh) at the neuromuscular junctions and synapses causes symptoms of both muscarinic and nicotinic toxicity. These include cramps, increased salivation, lacrimation, muscular weakness, paralysis, muscular fasciculation, diarrhea, and blurry vision.

How does acetylcholine work as a neurotransmitter?
In the PNS, acetylcholine is a major part of the somatic nervous system. Within this system, it plays an excitatory role leading to the voluntary activation of muscles. For example, the brain might send out a signal to move the right arm. The signal is carried by nerve fibers to the neuromuscular junctions.

How does acetylcholine make you feel?
Acetylcholine tells muscles to twitch and more, but it also tells your hippocampus to store a memory. It plays an essential role in alertness, attention, learning, and memory. It's so essential to memory, in fact, that acetylcholine deficits are associated with Alzheimer's disease.

Why acetylcholine is not used clinically?
Acetylcholine itself does not have therapeutic value as a drug for intravenous administration because of its multi-faceted action (non-selective) and rapid inactivation by cholinesterase.

Does acetylcholine affect mood?
Over 50 years ago, clinical studies suggested that increases in central acetylcholine could lead to depressed mood. Evidence has continued to accumulate suggesting that the cholinergic system plays a important role in mood regulation.

What mental disorder is associated with acetylcholine?
The cholinergic portion of the brain is the area of the brain that produces acetylcholine. Damage to this portion of the brain is linked to the development of Alzheimer's disease. Many people with Alzheimer's disease have altered levels of acetylcholine.

What is the relationship between dopamine and acetylcholine?
Abstract. It has been shown that dopamine inhibits the release of acetylcholine (ACh) from nerve terminals of caudate cholinergic interneurons, and the imbalance between dopaminergic and cholinergic system by 6-hydroxydopamine pretreatment leads to an increased ACh release.

How does acetylcholine affect Parkinson's?
Higher levels of acetylcholine are suggested to cause the dyskinesia — uncontrolled, involuntary movements — observed in Parkinson's patients under long-term dopamine therapy.

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Acetylcholine:
When high -> Parkinson's
When low -> Alzheimer's

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Trihexyphenidyl

Trihexyphenidyl is used to treat symptoms of Parkinson's disease or involuntary movements due to the side effects of certain psychiatric drugs (antipsychotics such as chlorpromazine/haloperidol). Trihexyphenidyl belongs to a class of medication called anticholinergics that work by blocking a certain natural substance (acetylcholine). This helps decrease muscle stiffness, sweating, and the production of saliva, and helps improve walking ability in people with Parkinson's disease. Anticholinergics can stop severe muscle spasms of the back, neck, and eyes that are sometimes caused by psychiatric drugs. It can also decrease other side effects such as muscle stiffness/rigidity (extrapyramidal signs-EPS). It is not helpful in treating movement problems caused by tardive dyskinesia and may worsen them.



Benadryl Tablet 

GENERIC NAME(S): Diphenhydramine Hcl

Diphenhydramine is an antihistamine used to relieve symptoms of allergy, hay fever, and the common cold. These symptoms include rash, itching, watery eyes, itchy eyes/nose/throat, cough, runny nose, and sneezing. It is also used to prevent and treat nausea, vomiting and dizziness caused by motion sickness. Diphenhydramine can also be used to help you relax and fall asleep.

This medication works by blocking a certain natural substance (histamine) that your body makes during an allergic reaction. Its drying effects on such symptoms as watery eyes and runny nose are caused by blocking another natural substance made by your body (acetylcholine).

References
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