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Adrenaline and its ligands

Category: Medicines

Type

Involuntary

Introduction and description

 

Adrenaline is also known as Epinephrine and adrenalin. It is a hormone and a neurotransmitter. It is the principle neurotransmitter in the sympathetic nervous system – so it stimulates our body and produces the fight or flight activity in us in response to high emotion, fear, stress and so on.

Adrenaline affects the heart rate, blood vessels and air passage diameters, metabolism, muscles, lungs, plus numerous other organs. The action is in line with what one would expect to help us 'fight or flight' – blood flow is diverted to key skeletal muscles from other muscles and glucose is pumped to those muscles in preference to others. Lungs dilate to take in more oxygen and allow us to run, blood vessels constrict to get the blood to muscles more quickly, the heart beats more strongly and we stop wanting to wee and poo, because this would be a little inconvenient on the run. The pupils dilate so we can see better to run if the light is not so good. And the penis becomes a little diddy thing, so that it doesn't get damaged in the ensuing battle [performance anxiety is indeed performance anxiety]

Background

 

Adrenaline is produced in some neurons of the central nervous system, and in the chromaffin cells of the adrenal medulla from the amino acids phenylalanine and tyrosine. In chemical terms, epinephrine is one of a group of monoamines called the catecholamines. There are five main adrenoceptors receptors

  • Alpha 1 receptor - controls the smooth muscle contraction of the bladder . The agonist action, being part of the sympathetic nervous system response will stop us wanting to pee and poo in order that we can ‘fight or flight’ more effectively
  • Alpha 2 receptor – This receptor controls vasoconstriction of veins and arteries, the result may be increased blood pressure . Because penises become erect when blood flows through them the vasoconstriction by default results in the little willy
  • Beta 1 – controls the smooth muscle contraction of the heart, heart rate increases and the heart beats more strongly to send the blood to the muscles
  • Beta 2 – controls the smooth muscle contraction of the lungs. Note that antagonists have the opposite effect to what you may think, constricting the airways. You could feel tight chested and short of breath with these. They are part of the parasympathetic nervous system in that once we are totally relaxed we have little need for as much oxygen, but they can also be aimed in nature at stopping you hyperventilating and breathing ‘bad airs’.

I have very much simplified the action in the headings above, concentrating on some key effects. 

Ligands

Agonists

Adrenaline and its ligands can supply us with hallucinations, visions, out of body experiences, near death and death. Thus agonists – the so called stimulants – at overdose levels have an effect. We will see how shortly. They can also cause permanent damage to your health in a relatively short time.

Examples of drugs in this category include Amitraz , Brimonidine , Cirazoline, Clonidine , Detomidine, Dexmedetomidine, Dobutamine, Formoterol, Guanfacine, Isoprenaline, Levalbuterol, Lofexidine , Medetomidine, Metaproterenol, Methoxamine, Noradrenaline, Phenylephrine, Ritodrine, Romifidine, Salbutamol, Salmeterol, Terbutaline, Tizanidine, Xylazine, Xylometazoline

Antagonists

The antagonists should in theory counteract the effects, but the natural endogenous chemicals that promote relaxation are adenosine and acetylcholine for example. Thus what one finds is that any antagonists are exogenous and very many are man-made. The exception is yohimbine [famous for its ability via better blood flow to improve erections].

Examples include Alfuzosin, Amitriptyline, Atenolol , Atipamezole, Butoxamine, Clomipramine, Doxazosin, Doxepin, Idazoxan , Metoprolol , Phenoxybenzamine, Phentolamine, Prazosin, Propranolol, Tamsulosin, Terazosin, Trimipramine

How it works

 

The majority of the time, spiritual experience is being caused by overdose resulting in hypoxia. The mind shuts down the reasoning function and memory as a first line of protection against the system failing, principally because reasoning and memory require considerable supplies of energy and that energy is needed to keep you alive in other areas! The main receptors that might contribute to spiritual experience and the reason is as follows: 

  • Alpha 2 – Agonists - constrict the veins and artries reducing the supply of blood to the brain. At overdose levels we could pass out, but if we don't the hypoxia may give us the experience.
  • Alpha 2 – Antagonists - cause vasodilation which in turn may lead to hypotension the veins and artries reducing the supply of blood to the brain. Again, at overdose levels we could pass out, but if we don't the hypoxia may give us the experience.
  • Beta 1 – Agonists – Beta 1 agonists increase the heart rate , and blood flow is diverted from other non-essential organs to skeletal muscle. You may feel hugely energised, even hyperactive, but with an over dose of these drugs, we may end up lacking oxygen to the brain. Take oxygen from the brain and the reason and memory function are affected.
  • Beta-1 Antagonists - decrease the heart rate which can lead to hypotension in someone who has a normal blood pressure or overdoses and from there we get hypoxia and a spiritual experience. You are likely to feel extremely sleepy and dopey going this route because of the lack of oxygen.
  • Beta 2 Agonistsare bronchodilators. They are used for the relief of conditions such as asthma. I think the spiritual experience caused by agonists are caused by over dosing – high doses and rapid administration. There then follows a chain of reactions. At extreme doses vasodilation occurs and the blood pressure falls. Meyer provides an example where 125 micrograms per minute reduced blood presure by 30mmHg. In effect you suffer from hypotension and hypotension can lead to hypoxia.
  • Beta 2 Antagonists  - have an opposite effect to the bronchodilators constricting the airways and again reducing oxygen leading to hypoxia. If you over dosed slightly on these, you could feel tight chested and short of breath. Not a particularly pleasant way to induce a spiritual experience – drug induced hypoxia/suffocation

Thus they all have much the same effect even though the chain of reactions is different in each case.

The alpha 1 products have no effect and will not produce a spiritual experience, but I have mentionned them to explain their action, so that you are aware of their existence.

References and further reading

There is an extremely useful chapter in Meyler’s side effects of drugs devoted to the side effects of all antianginal drugs alone and it does not make for comfortable reading. At least 22 pages are devoted to these drugs!

 

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