Candocuronium iodide (
INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
, formerly chandonium, HS-310)
is an
aminosteroid
Aminosteroids are a group of steroids with a similar structure based on an amino-substituted steroid nucleus. They are neuromuscular blocking agents, acting as competitive antagonists of the nicotinic acetylcholine receptor (nAChR), and block th ...
neuromuscular-blocking drug
Neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished via their action on the post-synaptic acetylcholine (Nm) receptors.
In cli ...
. Its use in
anesthesia for
endotracheal intubation
Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic tube into the trachea (windpipe) to maintain an open airway or to serve as a conduit through which to administer certain drugs. It is frequently ...
and to provide
skeletal muscle relaxation during
surgery or
mechanical ventilation
Mechanical ventilation, assisted ventilation or intermittent mandatory ventilation (IMV), is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move a ...
was briefly evaluated in clinical studies in India. However, further development was discontinued due to attendant cardiovascular effects, primarily
tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
that was about the same as the clinically established
pancuronium bromide
Pancuronium (trademarked as Pavulon) is an aminosteroid muscle relaxant with various medical uses. It is used in euthanasia and is used in some states as the second of three drugs administered during lethal injections in the United States.
Mecha ...
. Candocuronium demonstrated a short duration and a rapid onset of action, with little or no ganglion blocking activity, with a greater potency than pancuronium.
[
]
Background
As with other neuromuscular blocking agents, candocuronium preferentially antagonizes competitively the nicotinic
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...
subtype of acetylcholine receptors. The agent was developed by the laboratory of Harkishan Singh, Panjab University, Chandigarh, India, as part of the search for a non-depolarizing replacement for the most popular clinically used depolarizing agent, suxamethonium
Suxamethonium chloride, also known as suxamethonium or succinylcholine, or simply sux by medical abbreviation, is a medication used to cause short-term paralysis as part of general anesthesia. This is done to help with tracheal intubation or ele ...
(succinylcholine
Suxamethonium chloride, also known as suxamethonium or succinylcholine, or simply sux by medical abbreviation, is a medication used to cause short-term paralysis as part of general anesthesia. This is done to help with tracheal intubation or ele ...
).
Design of candocuronium
The ''mono''- and ''bis''-quaternary azasteroid series of compounds to which candocuronium belongs are based on the same principle that led to aminosteroids such as pancuronium
Pancuronium (trademarked as Pavulon) is an aminosteroid muscle relaxant with various medical uses. It is used in euthanasia and is used in some states as the second of three drugs administered during lethal injections in the United States.
Mec ...
, vecuronium
Vecuronium bromide, sold under the brand name Norcuron among others, is a medication used as part of general anesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation. It is also used to help with endotracheal in ...
and rocuronium
Rocuronium bromide (brand names Zemuron, Esmeron) is an aminosteroid non-depolarizing neuromuscular blocker or muscle relaxant used in modern anaesthesia to facilitate tracheal intubation by providing skeletal muscle relaxation, most commonly r ...
: use of the steroid skeleton to provide a somewhat rigid distance between the two quaternary ammonium centers, with appendages incorporating fragments of choline or acetylcholine. The discovery program initiated by Singh[ HS-347 was equipotent with tubocurarine but exhibited considerable ganglion blocking activity; candocuronium appeared to be suitably placed for clinical trials following encouraging preclinical evaluations.]
Modifications to the candocuronium design
Candocuronium did not provide the desired profile, and a further extension of research was undertaken to overcome its limitations. This led to four more potentially useful compounds, HS-692, HS-693, HS-704 and HS-705, whose onset and duration were indinguishable from candocuronium, but all demonstrated profound vagolytic effects and much weaker potencies than candocuronium.
Modifications at 3- and 16-positions of androstane nucleus
The discovery of candocuronium led to numerous related neuromuscular blocking agents with short durations of action but also having attendant undesirable cardiovascular effects. The Marshall group then explored other modifications at the 3- and 16-positions of the androstane nucleus,
References
External links
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{{DEFAULTSORT:Candocuronium Iodide
Muscle relaxants
Nicotinic antagonists
Quaternary ammonium compounds
Iodides
Pyrrolidines
Neuromuscular blockers