Obidoxime
Encyclopedia
Obidoxime is a member of the oxime
family used to treat nerve gas poisoning. Oximes are drugs known for their ability to reverse the binding of organophosphorus
compounds to the enzyme acetylcholinesterase
(AChE).
AChE is an enzyme that removes acetylcholine
from the synapse
after it creates the required stimulation on the next nerve cell. If it gets inhibited, acetylcholine is not removed after the stimulation and multiple stimulations are made, resulting in muscle contractions and paralysis
.
Organophosphate
s (such as nerve gases) are well known inhibitors of AChE. They bind to a specific place on the enzyme and prevent it from functioning normally by changing the OH group
on the serine
residue and by proton
ating (quaternary nitrogen
, R4N+) the nearby nitrogen atom located in the histidine
residue.
and asoxime (HI-6) are used to restore enzyme functionality. They have greater affinity for the organic phosphate residue than the enzyme and they remove the phosphate group, restore the OH to serine and turn nitrogen from histidine back into its R3N form (tertiary nitrogen). This results in full enzyme recovery and the phosphate-oxime compound is eliminated from the organism via urine
.
damage, kidney
damage, nausea
, vomiting, but they are very efficient antidote
s to nerve gas poisoning. Usually treatment of poisoning includes the use of atropine
, which can slow down the action of the poison, giving more time to apply the oxime.
Oxime
An oxime is a chemical compound belonging to the imines, with the general formula R1R2C=NOH, where R1 is an organic side chain and R2 may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substituted oximes form a closely related family of compounds...
family used to treat nerve gas poisoning. Oximes are drugs known for their ability to reverse the binding of organophosphorus
Organophosphorus
Organophosphorus compounds are degradable organic compounds containing carbon–phosphorus bonds , used primarily in pest control as an alternative to chlorinated hydrocarbons that persist in the environment...
compounds to the enzyme acetylcholinesterase
Acetylcholinesterase
"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...
(AChE).
AChE is an enzyme that removes acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
from the synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
after it creates the required stimulation on the next nerve cell. If it gets inhibited, acetylcholine is not removed after the stimulation and multiple stimulations are made, resulting in muscle contractions and paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
.
Organophosphate
Organophosphate
An organophosphate is the general name for esters of phosphoric acid. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA and RNA as well as many cofactors that are essential for life...
s (such as nerve gases) are well known inhibitors of AChE. They bind to a specific place on the enzyme and prevent it from functioning normally by changing the OH group
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
on the serine
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
residue and by proton
Proton
The proton is a subatomic particle with the symbol or and a positive electric charge of 1 elementary charge. One or more protons are present in the nucleus of each atom, along with neutrons. The number of protons in each atom is its atomic number....
ating (quaternary nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
, R4N+) the nearby nitrogen atom located in the histidine
Histidine
Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...
residue.
Function
Oximes such as obidoxime, pralidoximePralidoxime
Pralidoxime or 2-PAM, usually as the chloride or methiodide salts, belongs to a family of compounds called oximes that bind to organophosphate-inactivated acetylcholinesterase. It is used to combat poisoning by organophosphates or acetylcholinesterase inhibitors , in conjunction with atropine and ...
and asoxime (HI-6) are used to restore enzyme functionality. They have greater affinity for the organic phosphate residue than the enzyme and they remove the phosphate group, restore the OH to serine and turn nitrogen from histidine back into its R3N form (tertiary nitrogen). This results in full enzyme recovery and the phosphate-oxime compound is eliminated from the organism via urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
.
Side effects
Oximes like these do have side effects and they include liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
damage, kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
damage, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, vomiting, but they are very efficient antidote
Antidote
An antidote is a substance which can counteract a form of poisoning. The term ultimately derives from the Greek αντιδιδοναι antididonai, "given against"....
s to nerve gas poisoning. Usually treatment of poisoning includes the use of atropine
Atropine
Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...
, which can slow down the action of the poison, giving more time to apply the oxime.