Cholinergic | Definition, Effects, and Function

What is Cholinergic?

Cholinergic is a term used to refer to the acetylcholine molecule. It’s usually used to define neurons, receptors, or synapses that use acetylcholine. For example, a cholinergic neuron is a neuron that releases acetylcholine, and a cholinergic receptor is a receptor to which acetylcholine binds.

Acetylcholine is a signaling molecule in the nervous system that is used by nerve cells to transmit information. It is widespread in the peripheral nervous system, which is involved in the contraction of skeletal and smooth muscles and the widening of blood vessels, among other things.

Acetylcholine plays an important role in the neuromuscular junction, i.e. At the joint between nerve cells and muscle. In addition, acetylcholine is also present in the central nervous system, where it plays a role in cognitive processes such as memory, learning, and arousal.

Unsurprisingly, its role in numerous processes of the peripheral and central nervous system has made the cholinergic system a target in the treatment of multiple diseases. In turn, several cholinergic drugs have been developed for both clinical and cosmetic purposes.

For example, some cholinergic drugs are used to treat severe muscle spasms, others to slow the progression of Alzheimer’s disease, and others to reduce wrinkles. However, in addition to therapeutic and cosmetic effects, cholinergic drugs can cause a number of side effects, including paralysis of the autonomic nervous system.


Acetylcholine Function

Acetylcholine is the major 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 body secretion and slows the heart rate.

Acetylcholine is present in the peripheral and central nervous systems. In the peripheral nervous system, acetylcholine is primarily involved in muscle movement and other functions such as widening blood vessels. It is involved in cognitive functions in the central nervous system.

Acetylcholine binds to cholinergic receptors, the two main types of which are muscarinic and nicotine. Muscarinic acetylcholine receptors (mAChR) are G-protein coupled receptors (GPCR) that modulate the activity of the cell by activating cellular mechanisms in which second messengers are involved.

Here are five identified types are known as M1 to M5. M1, M3, and M5 muscarinic receptors are usually excitatory and of the Gq type; Therefore, they fulfill their function by activating phospholipase C (PLC), which in turn activates the IP3 signal transduction cascade and enables the release of calcium in intracellular stores into the cytosol.

M2 and M4 receptors are usually inhibitory and of the Gi– or Go-type, i.e. They work by reducing cyclic AMP (cAMP) in the cell. Nicotinic acetylcholine receptors (nAChR), the other major type, are ligand-gated ion channels that, when activated by acetylcholine, allow ions to directly enter (e.g., sodium) or exit (e.g., potassium) the cell.

Acetylcholine in the Peripheral Nervous System

Acetylcholine plays an important role in the neuromuscular junction. The neuromuscular junction is where a nerve cell (a neuron) and skeletal muscle (the type of muscle that contracts voluntarily) are connected.

In order for a muscle to contract, the brain sends electrochemical signals from one neuron to another until an action potential (electrical signal) is generated at the motor neuron, the neuron that touches the muscle fiber.

At the neuromuscular junction, acetylcholine is released from the motor neuron into the synaptic cleft, which then binds to nicotinic acetylcholine receptors that are present on the muscle fiber cell. Nicotine acetylcholine receptors allow sodium to enter the muscle cell, after which a series of intracellular signals causes the muscle to contract.

Peripheral cholinergic transmission abnormalities have been linked to motor disorders such as myasthenia gravis, a disorder characterized by fatigue and muscle weakness.

Acetylcholine is also a widely used neurotransmitter in the autonomic nervous system – a part of the peripheral nervous system that is involved in the control of unconscious and involuntary body functions.

In particular, acetylcholine is released by neurons of a central nervous system that project to neurons of the autonomic nervous system, the latter of which detect acetylcholine via nicotinic acetylcholine receptors.

These neurons, in turn, project onto parts of the body that are not part of the nervous system, such as the gastrointestinal tract. In some cases, acetylcholine is also released at this junction between the peripheral nervous system and other parts of the body.

Acetylcholine in the Central Nervous System

In the central nervous system, cholinergic activity is related to arousal, awareness, learning, memory, attention, and reward, among other things. Unsurprisingly, abnormal cholinergic transmission has been linked to Alzheimer’s disease, a neurodegenerative disease characterized by memory loss.

Cholinergic Drugs

The involvement of acetylcholine in nervous system disorders has naturally made the cholinergic system a target for therapeutic purposes. Drugs that activate (agonists) or inactivate (antagonists) acetylcholine receptors, as well as drugs that modulate cholinergic activity by facilitating or preventing the production, release, or breakdown of acetylcholine, have been developed with the aim of treating several neuropsychiatric disorders.

Acetylcholine Agonists

Acetylcholine has a very short lifespan: it does not last long in the bloodstream because it is broken down very quickly. Therefore, acetylcholine itself is not used as a drug, but similar compounds are used that activate acetylcholine receptors to activate them. These similar compounds that bind to and activate acetylcholine receptors are known as acetylcholine agonists.

An example of an agonist is pilocarpine, which activates muscarinic receptors and is usually used in the pupil of the eye to treat a neurodegenerative disease that causes blindness called glaucoma. Another example of an agonist is nicotine, which is found in tobacco.


Many cholinergic drugs are acetylcholine receptor antagonists, which block acetylcholine receptors. Some antagonists are atropine, scopolamine, hexamethonium, and trimethaphane.

Atropine and scopolamine inactivate muscarinic receptors and are used to suppress body secretions (e.g., tears or mucus) and to relax smooth muscles (e.g., muscles in the gastrointestinal tract) during anesthesia and to treat motion sickness.

Hexamethonium and trimethaphane block nicotine receptors and are used to lower high blood pressure. Other agents that block nicotine receptors are used because of their action at the neuromuscular junction; These agents prevent skeletal muscle contraction and are often used during surgery to prevent patients from making involuntary movements.

Other Drugs

In addition to cholinergic agonists and antagonists, other drugs can modulate acetylcholine activity by increasing or decreasing its production, release, or breakdown. For example, inactivating acetylcholine transferase, an enzyme that breaks down acetylcholine, is used to increase acetylcholine levels and treat myasthenia gravis, a neuromuscular disorder.

Similar drugs such as neostigmine and pyridostigmine do not cross the blood-brain barrier and are therefore used to exert their effects on the neuromuscular junction and to contract the skeletal muscle.

Still, anticholinergics – drugs that reduce or block the effects of acetylcholine – are more commonly used to treat a variety of conditions. Some of these are involuntary movements, gastrointestinal disorders, incontinence, and Parkinson’s disease.

Another compound that blocks the release of acetylcholine is botulinum toxin – an active ingredient produced by a type of bacterium – which paralyzes skeletal muscles so that the body can no longer move and can even be fatal.

When applied locally, the botulinum toxin relaxes the muscles and is therefore used to treat severe muscle spasms. The same compound is used to reduce wrinkles by relaxing the muscles and skin. We know this under the trade name Botox.

Cholinergic Effects

The effects of activating cholinergic receptors include muscle contraction, heart rate delay, constriction of the iris (miosis) and lens, mucus secretion, and bronchoconstriction.

Conversely, the effects of inactivating cholinergic receptors include muscle relaxation, increased heart rate, pupil dilation (mydriasis) and lens flattening (cyclopegia), dryness of the upper airways (respiratory tract), inhibition of tear production, urine retention, dry mouth, slowing down of mucociliary muscle activity Skeletal and smooth muscles).

Side Effects of Cholinergic Drugs

Cholinergic drugs can help treat some disorders and relieve symptoms, but they also have negative side effects. Most cholinergic drugs are anticholinergics, i.e. They decrease or block the effects of acetylcholine.

For example, the acetylcholine antagonists hexamethonium and trimethaphane, which are used to treat high blood pressure, can cause paralysis of the autonomic nervous system, resulting in effects such as blurred vision and inability to urinate.

Anticholinergics can generally cause body temperature to rise as they decrease sweating. They can also cause drowsiness, hallucinations, confusion, dry mouth, constipation, difficulty urinating, and impaired memory.

The elderly can cause confusion, memory loss, and cognitive decline. Mixing anticholinergics with alcohol has side effects similar to overdosing on anticholinergics, including dizziness, fever, confusion, increased heart rate, difficulty breathing, hallucinations, loss of consciousness, and even death. Caution should therefore be exercised when taking cholinergic drugs.

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