Parasympathomimetics
Encyclopedia
A parasympathomimetic drug is a drug
or poison
that acts by stimulating or mimicking the parasympathetic nervous system
(PSNS). These chemicals are also called cholinergic
drugs because acetylcholine
(ACh) is the neurotransmitter
used by the PSNS. Chemicals in this family can act either directly by stimulating the nicotinic
or muscarinic
receptors, or indirectly by inhibiting cholinesterase
, promoting acetylcholine release, or other mechanisms.
Some chemical weapons such as sarin
or VX
, non-lethal riot control agents such as tear gas
, and insecticides such as diazinon
fall into this category.
or muscarinic
receptors.
.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
or poison
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....
that acts by stimulating or mimicking the parasympathetic nervous system
Parasympathetic nervous system
The parasympathetic nervous system is one of the two main divisions of the autonomic nervous system . The ANS is responsible for regulation of internal organs and glands, which occurs unconsciously...
(PSNS). These chemicals are also called cholinergic
Cholinergic
The word choline generally 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...
drugs because acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
(ACh) is the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
used by the PSNS. Chemicals in this family can act either directly by stimulating the nicotinic
Nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the postsynaptic side of the neuromuscular junction...
or muscarinic
Muscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
receptors, or indirectly by inhibiting cholinesterase
Cholinesterase
In biochemistry, cholinesterase is a family of enzymes that catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation.-Types:...
, promoting acetylcholine release, or other mechanisms.
Some chemical weapons such as sarin
Sarin
Sarin, or GB, is an organophosphorus compound with the formula [2CHO]CH3PF. It is a colorless, odorless liquid, which is used as a chemical weapon. It has been classified as a weapon of mass destruction in UN Resolution 687...
or VX
VX (nerve agent)
VX, IUPAC name O-ethyl S-[2-ethyl] methylphosphonothioate, is an extremely toxic substance whose only application is in chemical warfare as a nerve agent. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations in UN Resolution 687...
, non-lethal riot control agents such as tear gas
CS gas
2-chlorobenzalmalononitrile is the defining component of a "tear gas" commonly referred to as CS gas, which is used as a riot control agent...
, and insecticides such as diazinon
Diazinon
Diazinon , a colorless to dark brown liquid, is a thiophosphoric acid ester developed in 1952 by Ciba-Geigy, a Swiss chemical company...
fall into this category.
Structure activity relationships for parasympathomimetic drugs
For a cholinergic agent, the following criteria describe the structure activity relationship:- Ing's Rule of 5: There should be no more than five atoms between the nitrogen and the terminal hydrogen for Muscarinic (or cholinergic) activity.
- 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.
- There should be a two-carbon unit between the oxygen atom and the nitrogen atom.
Direct-acting
These act by stimulating the nicotinicNicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the postsynaptic side of the neuromuscular junction...
or muscarinic
Muscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
receptors.
- Choline esters
- AcetylcholineAcetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
(all acetylcholine receptors) - BethanecholBethanecholBethanechol is a parasympathomimetic choline carbamate that selectively stimulates muscarinic receptors without any effect on nicotinic receptors. Unlike acetylcholine, bethanechol is not hydrolyzed by cholinesterase and will therefore have a long duration of action. Bethanechol does not involve...
(M3 receptors) - CarbacholCarbacholCarbachol , also known as carbamylcholine, is a drug that binds and activates the acetylcholine receptor. Thus it is classified as a cholinergic agonist. It is primarily used for various ophthalmic purposes, such as for treating glaucoma, or for use during ophthalmic surgery...
(all muscarinic receptors and some nicotinic receptors) - Methacholine (all muscarinic receptors)
- Acetylcholine
- Plant alkaloids
- ArecolineArecolineArecoline is an alkaloid natural product found in the areca nut, the fruit of the areca palm . It is an odourless oily liquid volatile in steam, miscible with most organic solvents and water, but extractable from the latter by ether in presence of dissolved salts. The salts are crystalline, but...
- NicotineNicotineNicotine is an alkaloid found in the nightshade family of plants that constitutes approximately 0.6–3.0% of the dry weight of tobacco, with biosynthesis taking place in the roots and accumulation occurring in the leaves...
- MuscarineMuscarineMuscarine, L--muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of muscarine which can be dangerous if ingested...
- PilocarpinePilocarpinePilocarpine is a parasympathomimetic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, which acts therapeutically at the muscarinic acetylcholine receptor M3 due to its...
(M3 receptors)
- Arecoline
Indirect-acting
Indirect acting parasympathomimetic drugs may be either reversible cholinesterase inhibitors, irreversible cholinesterase inhibitors or drugs that promote ACh release or anti-adrenergics. The latter inhibits the antagonistic system, the sympathetic nervous systemSympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
.
- Reversible cholinesterase inhibitors
- DonepezilDonepezilDonepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the palliative treatment of mild to moderate Alzheimer's disease. Common side effects include...
- EdrophoniumEdrophoniumEdrophonium is a readily reversible acetylcholinesterase inhibitor. It prevents breakdown of the neurotransmitter acetylcholine and acts by competitively inhibiting the enzyme acetylcholinesterase, mainly at the neuromuscular junction...
- NeostigmineNeostigmineNeostigmine is a parasympathomimetic that acts as a reversible acetylcholinesterase inhibitor.- Synthesis :Neostigmine was first synthesized by Aeschlimann and Reinert in 1931....
- PhysostigminePhysostigminePhysostigmine is a parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean....
- PyridostigminePyridostigminePyridostigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. Since it is a quaternary amine, it is poorly absorbed in the gut and does not cross the blood-brain barrier, except possibly in stressful conditions.-Mode of action:...
- RivastigmineRivastigmineRivastigmine is a parasympathomimetic or cholinergic agent for the treatment of mild to moderate dementia of the Alzheimer’s type and dementia due to Parkinson's disease. The drug can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which...
- TacrineTacrineTacrine is a centrally acting anticholinesterase and indirect cholinergic agonist . It was the first centrally-acting cholinesterase inhibitor approved for the treatment of Alzheimer's disease, and was marketed under the trade name Cognex. Tacrine was first synthesised by Adrien Albert at the...
- Donepezil
- Irreversible cholinesterase inhibitors
- EchothiophateEchothiophateEchothiophate is a parasympathomimetic and a phosphorothioate. It is an acetylcholinesterase inhibitor.- Uses :It is used as an ocular antihypertensive in the treatment of chronic glaucoma and, in some cases, accommodative esotropia...
- Isoflurophate
- MalathionMalathionMalathion is an organophosphate parasympathomimetic which binds irreversibly to cholinesterase. Malathion is an insecticide of relatively low human toxicity, however one recent study has shown that children with higher levels of organophosphate pesticide metabolites in their urine are more likely...
- Echothiophate
- ACh release promoters
- CisaprideCisaprideCisapride is a gastroprokinetic agent, a drug which increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic. Stimulation of the serotonin receptors increases acetylcholine release in the enteric nervous...
- MetoclopramideMetoclopramideMetoclopramide is an antiemetic and gastroprokinetic agent. It is commonly used to treat nausea and vomiting, to facilitate gastric emptying in people with gastroparesis, and as a treatment for the gastric stasis often associated with migraine headaches.-Medical uses:Metoclopramide is commonly...
- Cisapride
- Anti-adrenergics
- clonidineClonidineClonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
(α-receptor agonistAgonistAn agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
, α2 > α1, giving negative feedbackNegative feedbackNegative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
) - methyldopaMethyldopaMethyldopa is an alpha-adrenergic agonist psychoactive drug used as a sympatholytic or antihypertensive. Its use is now mostly deprecated following the introduction of alternative safer classes of agents...
(α2Alpha-2 adrenergic receptorThe alpha-2 adrenergic receptor is a G protein-coupled receptor associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well...
agonist, giving negative feedbackNegative feedbackNegative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
) - propranolol (β-receptor antagonistAntagonistAn antagonist is a character, group of characters, or institution, that represents the opposition against which the protagonist must contend...
) - atenolol (β1Beta-1 adrenergic receptorThe beta-1 adrenergic receptor , also known as ADRB1, is a beta-adrenergic receptor, and also denotes the human gene encoding it...
antagonist) - prazosinPrazosinPrazosin, trade names Minipress, Vasoflex, Pressin and Hypovase, is a sympatholytic drug used to treat high blood pressure and Anxiety, PTSD and Panic Disorder. It belongs to the class of alpha-adrenergic blockers. Specifically, prazosin is selective for the alpha-1 receptors on vascular smooth...
(α1Alpha-1 adrenergic receptorThe alpha-1 adrenergic receptor is a G protein-coupled receptor associated with the Gq heterotrimeric G-protein. It consists of three highly homologous subtypes, including α1A-, α1B-, and α1D-adrenergic...
antagonist)
- clonidine