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Suppression

Muscarine and the muscarinic ligands

Category: Natural chemicals

Type

Voluntary

Introduction and description

Betel nuts are a source for muscarinic ligands

Acetylcholine and its ligands control the parasympathetic nervous system, the opposite system to the ‘fight and flight system’ that is the sympathetic nervous system. 

Thus through this system, acetylcholine and its ligands, we can promote absolute relaxation of our nerves, our muscles, and our mind. 

There are two types of cholinergic receptors – the nicotinic and the muscarinic. 

  • Nicotinic receptors – are found on skeletal muscle and at nerve synapses, so named because Nicotine is one major natural ligand of this receptor
  • Muscarinic receptors – are found on smooth and cardiac muscle, so named because Muscarine is a major ligand of this receptor

Acetylcholine acts on all the receptors – both nicotinic and muscarinic, but you can’t administer acetylcholine as it is an endogenous [in the body] chemical.  If given orally it is hydrolysed in the stomach by acid catalysis.  You can’t inject it either, as it is hydrolysed in the blood both chemically and by enzymes [sterases].

Thus, if you are going to invoke the parasympathetic system and all its healing potential you use either nicotine, which can actually be found in a number of plants, but is of course best known in tobacco, and ligands of the muscarinic receptors and more specifically the plants they are found in.

Muscarinic receptors - M AChRs

a relaxed radish from the choline .................

There are 5 different types of muscarinic receptors; M1 - M5, and most tissues express a mixture of subtypes. The M2 and M3 subtypes mediate muscarinic responses at peripheral autonomic tissues. M1 and M4 subtypes are more abundant in brain and autonomic ganglia.

  • M1 receptor – this receptor controls the secretions from our salivary glands and our stomach, as well as affectig the functions of memory.  Antagonists– the substances deactivating these functions are atropine, scopolamine, dicycloverine, tolterodin, oxybutynin, ipratropiu, mamba toxin MT7, pirenzepine, telenzepine
  • M2 receptor – this receptor has functions that slow heart rate, ‘reduce the contractile forces of the atrium’ meaning the chamber in which blood enters the heart, ‘reduces conduction velocity of AV node’ - atrial and ventricular chambers of the heart; activates target enzymes and acts on the central nervous system.   Antagonists – the substances blocking  these functions are atropine, dicycloverine, tolterodine, oxybutynin, ipratropium, methoctramine, tripitamine, gallamine
  • M3 receptor – this receptor controls smooth muscle contraction, “increases intracellular calcium in vascular endothelium”, increases endocrine and exocrine gland secretions, e.g. salivary glands and stomach; has central nervous system effects; controls the focussing of the eye, and vasodilation [dilation of veins and arteries].   Antagonists - the substances blocking  these functions are atropine, dicycloverine,  tolterodine, oxybutynin, ipratropium, darifenacin, tiotropium
  • The M4 receptor – activation of M4 causes increased or decreased locomotion via the brain  Antagonists – the substances blocking  these functions are atropine, dicycloverine,  tolterodine, oxybutynin, ipratropium, mamba toxin MT3

The functions of the muscarinic receptors

Concentrated tomato products are a good source of choline

Nicotine and other nicotinic receptor ligands are active at the synapses between different neurons and also at the synapses between neurons and skeletal muscle, but have poor activity elsewhere

Muscarine and the other muscarinic ligands are active at the synapses of neurons with smooth muscle but shows poor activity at sites where nicotine is active.

Medicinally, therefore one would choose muscarinic ligands for smooth muscle problems.

Where are smooth muscles to be found?

  • The stomach is a smooth muscle – thus to help with digestion and stomach  problems, muscarinic agents may be an answer
  • The heart is a smooth muscle – thus one would choose muscarinic agents to help slow the heart rate and sort out the flutters and arrythmias of stress, to take away the pressure on the heart from too much adrenaline
squashes are a good source of choline

Wikipedia
The M2 muscarinic receptors are located in the heart, where they act to slow the heart rate down to normal sinus rhythm after stimulatory actions of the sympathetic nervous system, by slowing the speed of depolarization. They also reduce contractile forces of the atrial cardiac muscle, and reduce conduction velocity of the atrioventricular node (AV node). It also serves to slightly decrease the contractile forces of the ventricular muscle.

 

  • The intestines – have a smooth muscle component, as such you can help with what is called peristalsis, the movement of food through the intestine.  Again this helps in overall digestion and also helps with constipation.
  • The bladder – the bladder is a smooth muscle and once relaxation sets in you may want to wee quite quickly
  •  
    The eyes are smooth muscles – thus there may be an opportunity to help with eye strain.  We tend not to realise that our eyes are often damaged by trying to work at close quarters the whole time.  Constant close work or play on computers or books requires the eye to focus and pull in the muscles, contract them.  Our eyes were actually made for seeing at distance.  This is why the eyesight of African native peoples is so good when they are not forced to go to school.  Once they are put in school, with its endless bookwork and close work, they end up having to wear glasses, just like we do
  • The lungs are smooth muscle – in the non flight or fight mode, the lungs are actually quite relaxed because we don’t need as much oxygen from being relaxed.  Thus there may be an opportunity here to help anyone who ‘overbreathes’ from stress – those who have panic attacks, for example.  Asthma is a condition involving a number of possible causes, including pathogens, but where the cause is stress, distress and fear, then again muscarinic agents may be a useful medicine
  • The blood circulatory system veins and arteries are smooth muscles and here we have a possibility for vasodilation of quite a profound nature.  “activation of M3 on vascular endothelial cells causes increased synthesis of nitric oxide, which diffuses to adjacent vascular smooth muscle cells and causes their relaxation, thereby explaining the paradoxical effect of parasympathomimetics on vascular tone and bronchiolar tone
  • The liver and pancreas plus some other exocrine glands work via smooth muscle.  Again muscarinic agents should help with digestion, but as the liver has a major role in ridding us of toxins and other unwanted substances or pathogens, then application of muscarinic ligands at times of stress may help a lot.  Does it help with diabetes or not?  We don’t know.  It depends on the cause of the diabetes, but it may help or may not.  Insulin is primarily mediated by M3-muscarinic receptors

Wikipedia
Exocrine glands are glands that produce and secrete substances onto an epithelial surface by way of a duct. Examples of exocrine glands include sweat, salivary, mammary [breast], ceruminous [ear wax], lacrimal [tears], sebaceous [skin oils], and mucous [penis, vagina, etc]. The liver and pancreas are both exocrine and endocrine glands; they are exocrine glands because they secrete products—bile and pancreatic juice—into the gastrointestinal tract through a series of ducts, and endocrine because they secrete other substances directly into the bloodstream

 

As you can see from the list from Wikipedia of all the functions of the exocrine glands, quite a number of problems have the potential of being helped here – inability to sweat, dry mouth, dry eyes, dry skin, a vagina without lubrication, a penis without lubrication. 

It is worth noting that men can have erections in the mornings after a night’s sleep because they are very relaxed, the parasympathetic system in full operation. 

They don’t get an ejaculation because it takes an excitatory response to get the ejaculation.  In effect, the invocation of the parasympathetic nervous system helps with erectile dysfunction and, as long as you can keep calm, prevents premature ejaculation.

Muscarinic agents and the central nervous system

Muscarinic agents also acts on the central nervous system.  They act via all receptors M1, M2, M3, M4 and M5, as these are found in the Central nervous system and peripheral nervous system.

 

One thing they do, is mentally relax us.  They stop the buzz buzz buzz of the over active mind. 

Despite the obvious fear of those who live by their memory alone that this is somehow going to inhibit their abilities, it actually does the opposite.

Going round and round in your own memory is generally of no help whatsoever in solving problems.  You might be able to appear on mastermind, recalling what you have stored away, but confronted with a new problem, you are going to be a failure. 

By relaxing in a major way we become open to inspiration and wisdom.  It is only by being laid back and going with the flow, that you ever get ‘the truth’.  Muscarinic agents open the door.

They also have an effect on the centres of the brain that control ‘locomotor activity’.  If we are going to relax, then all of us needs to be relaxed and muscarinic agents here may act as a general slower of twitching and involuntary muscle seizures.  So it may help with Tourette’s.

Pilocarpus grandiflorus

 

The muscarinic agents

The main naturally occurring muscarinic agonists are as follows : 

Chemical

M1

M2

M3

M4

M5

Acetylcholine [endogenous]

x

x

x

x

x

Muscarine [naturally occurring in mushrooms]

x

x

x

x

x

Pilocarpine [naturally occurring in a shrub]

x

x

x

x

X

Arecoline and Arecaidine [naturally occurring in betel nut]

x

x

x

x

 

Choline

x

x

x

x

x

 

  •  
    Pilocarpine is a drug used medically to treat dry mouth and glaucoma. It is obtained from the leaves of tropical South American shrubs from the genus Pilocarpus. It is a non-selective muscarinic receptor agonist in the parasympathetic nervous system, but is generally only used therapeutically at the muscarinic acetylcholine receptor M3 due to its topical application, e.g., in glaucoma and xerostomia.
  • Muscarine -  L-(+)-muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species. Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of muscarine. Muscarine has been found in trace amounts in Boletus, Hygrocybe, Lactarius and Russula. Muscarine is also a trace compound in the fly agaric Amanita muscaria; it may actually be via this trace amount that much of its observed activity is exerted.  Most research has been aimed at the chemicals with larger amounts – notably muscimol. A. muscaria fruitbodies contain a variable dose of muscarine, usually around 0.0003% fresh weight. Inocybe and Clitocybe contain muscarine concentrations up to 1.6%.
  • Arecoline and arecaidine  -  are alkaloids found in the areca nut, commonly known as the betel nut, the fruit of the areca palm (Areca catechu).  
  • Choline – Choline is found in a number of things we class as food.  We have a detailed description of choline on the site, because of its importance

There are a number of man made drugs, which are being used in research eg Sabcomeline that are of little interest to this site, as we aim to use natural products integrated in Nature.

Overload

 

Ignoring the man made drugs, it would appear that the natural agonists for the muscarinic receptors share a similar profile to Nicotine.  Nicotine is exceptionally poisonous if taken in anything larger than a trace amount.  If you look at its description in the context of Tobacco or more especially the Smoking addiction treatments, you will see that it can kill very quickly if ingested in anything like a ‘normal dose’.  The only reason it is safe to smoke cigarettes, is because most of the chemical is vapourised and never reaches the person at all.  It has  considerable therapeutic potential, but the amounts have to be homeopathic in size to be safe.

And so it appears to be the same with these chemicals. The amount of muscarine in the Inocybe and Clitocybe mushrooms, if simply ingested as if they were just mushrooms is way way too high and produces extremes of the functions shown above ie

  • The stomach– nausea and vomiting
  • The heart –slowing of the heartrate to dangerous levels - bradycardia
  • The intestines – diarrhoea, often quite violent diarrhoea with cramp.
  • The bladder – “there is a painful urge for urination”
  • The eyes– blurred vision, miosis  
  • The lungs – dangerously low levels of oxygen intake, almost complete depression of lung function
  • The blood circulatory system – so much vasodilation the heart goes all a flutter trying to fill the veins and arteries and a serious drop in blood pressure – hypotension.  There may be headaches because inadequate blood is getting to the brain
  • The liver and pancreas – there appears to have been little research done here,  and we do not wish to speculate. 

And via the other exocrine glands - increased salivation, excessive sweating, lacrimation [profuse tears], oily secretions for the skin, a large amount of mucous in private parts.  Dribbling.

And there are often hallucinations caused by the hypoxia and changes in neuronal activity.

“Death after 8 to 9 hours has been reported in about 5% of the cases, but can be avoided completely by prompt diagnosis and treatment with atropine”.  

So as we can see over stimulation of the parasympathetic nervous system can be as dangerous as over stimulation of the sympathetic nervous system

Method

Boletus - an edible mushroom

Choline is found in foods, whereas  muscarine, pilocarpine, arecoline and nicotine are to be found in medicinal plants, as such there is a complementary system in operation here.

Maintaining balance

To maintain the parasympathetic system in balance we use choline containing foods.  The choline in foods is converted in the body by the acetyl coenzyme A to acetylcholine, our endogenous relaxation promoter.  Methionine containing foods can also help, as in times of choline shortage, the body is able to use the Methionine in food to create choline.

Correcting imbalance

 

But at times of great imbalance, when we are stressed out of our trees, or in enormous pain from a long lasting wound, or tense with high blood pressure and exhausted, palpitating wildly with arrhythmias and heart flutter, wide eyed and over stimulated, then medicine is needed and nicotine and the muscarinic agents can be brought into play.

We have discussed the role of nicotine and the correct usage under three headings on the site – tobacco [no more smoking though!!] , horsetail and smoking addiction treatments

Discussion of the uses of muscarinic agents is via each plant and we have concentrated on only a few whose roles are discussed via observations, rather than actual entries.  We consider:

  • Boletus mushrooms -  which are edible, to be of interest and
  • Pilocarpus - whose activities do not seem to have been explored sufficiently nor its full potential understood

The Betel nut is well known, but its effect on teeth and gums leaves  a lot to be desired!

The reasons why we do not favour the other mushrooms is best explained by this extract:

Inocybe is a large, complex genus of mushrooms. Members of Inocybe are mycorrhizal, and some evidence shows that the high degree of speciation in the genus is due to adaptation to different trees and perhaps even local environments.
Inocybe species are not considered suitable for consumption. Many species contain large doses of muscarine, some less so but it is worth pointing out that Inocybe is the most commonly-encountered mushroom genus for which microscopic characteristics are the only means of certain identification to the species level.
In other words it takes an expert with a microscope to identify them.
The vast majority of Inocybes are considered poisonous because of the very high levels of muscarine they contain.  Furthermore, seven rare species of Inocybe contain psilocybin, but distinguishing them from the other varieties also requires expert help.  These include:

  • Inocybe aeruginascen [ which also contains aeruginascine]
  • Inocybe corydalina var. corydalina
  • Inocybe calamistrata
  • Inocybe coelestium
  • Inocybe corydalina var. erinaceomorpha 
  • Inocybe haemacta
  • Inocybe tricolor

 

Related observations