Hexamethonium
Encyclopedia
Hexamethonium is a ganglionic blocker
, a nicotinic nACh
(NN) receptor antagonist
that acts in autonomic ganglia by binding mostly in or on the NN receptor, and not the acetylcholine
binding site itself. It does not have any effect on the muscarinic acetylcholine receptors (mAChR) located on target organs of the parasympathetic nervous system
but acts as antagonist at the nicotinic acetylcholine receptors located in sympathetic and parasympathetic ganglia (NN) .
(noradrenaline) (adrenergic receptors), whereas parasympathetic systems are acetylcholine-based, and instead rely on muscarinic receptors (some post-ganglionic sympathetic neurons, such as those stimulating sweat glands, release acetylcholine).
The organ system and adverse effects of ganglion blockers are due to the parasympathetic and sympathetic stimuli blockage at preganglionic sites. Side-effects include combined sympatholytic
(e.g., orthostatic hypotension
and sexual dysfunction
) and parasympatholytic
(e.g., constipation, urinary retention
, glaucoma
, blurry vision, decreased lacrymal secretion, dry mouth (xerostomia
)) effects.
, of the peripheral nervous system
, which is innervated only by the sympathetic nervous system
. The non-specificity of this treatment led to discontinuing its use.
The use of inhaled hexamethonium, an unapproved drug, in a normal volunteer during a medical study is believed to have caused or contributed to her death in light of the presence of abnormal "ground glass opacities" on her chest X-ray.
Ganglionic blocker
A ganglionic blocker is a type of medication that inhibits postganglionic transmission, primarily by acting as a nicotinic antagonist....
, a nicotinic nACh
Acetylcholine receptor
An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.-Classification:...
(NN) receptor antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
that acts in autonomic ganglia by binding mostly in or on the NN receptor, and not the acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
binding site itself. It does not have any effect on the muscarinic acetylcholine receptors (mAChR) located on target organs of 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...
but acts as antagonist at the nicotinic acetylcholine receptors located in sympathetic and parasympathetic ganglia (NN) .
Pharmacology
It can act on receptors at pre-ganglionic sites in both the sympathetic and parasympathetic nervous systems, which are both regulated by nicotinic ligand-gated ionotropic acetylcholine receptors. Postganglionic sympathetic systems are usually regulated by norepinephrineNorepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(noradrenaline) (adrenergic receptors), whereas parasympathetic systems are acetylcholine-based, and instead rely on muscarinic receptors (some post-ganglionic sympathetic neurons, such as those stimulating sweat glands, release acetylcholine).
The organ system and adverse effects of ganglion blockers are due to the parasympathetic and sympathetic stimuli blockage at preganglionic sites. Side-effects include combined sympatholytic
Sympatholytic
A sympatholytic drug is a medication which inhibits the postganglionic functioning of the sympathetic nervous system . They are indicated for various functions, for example they may be used as antihypertensives...
(e.g., orthostatic hypotension
Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...
and sexual dysfunction
Sexual dysfunction
Sexual dysfunction or sexual malfunction refers to a difficulty experienced by an individual or a couple during any stage of a normal sexual activity, including desire, arousal or orgasm....
) and parasympatholytic
Parasympatholytic
A parasympatholytic agent is a substance or activity that reduces the activity of the parasympathetic nervous system. A parasympatholytic agent is a substance or activity that reduces the activity of the parasympathetic nervous system. A parasympatholytic agent is a substance or activity that...
(e.g., constipation, urinary retention
Urinary retention
Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
, glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
, blurry vision, decreased lacrymal secretion, dry mouth (xerostomia
Xerostomia
Xerostomia is the medical term for the subjective complaint of dry mouth due to a lack of saliva. Xerostomia is sometimes colloquially called pasties, cottonmouth, drooth, or doughmouth. Several diseases, treatments, and medications can cause xerostomia. It can also be exacerbated by smoking or...
)) effects.
Uses
It was formerly used to treat disorders, such as chronic hypertensionHypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, of the peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
, which is innervated only by the sympathetic nervous system
Sympathetic 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...
. The non-specificity of this treatment led to discontinuing its use.
The use of inhaled hexamethonium, an unapproved drug, in a normal volunteer during a medical study is believed to have caused or contributed to her death in light of the presence of abnormal "ground glass opacities" on her chest X-ray.