Double-sided angel - ketamine's tortuous research and development path

Wen: The story should also start from cyclhexamine, as an industrial product, has an anesthesia effect, but is toxic, not suitable as an anesthetic.
1950s, the war continued, especially when the United States launched the Vietnam War in 1955.
and good anesthetics have always been scarce, especially in those days.
a company called Park Davis, decided to develop anaesthetic.
they started with cyclohetamine and used Gert's reagents to synthesize a total of 60 compounds of phencyclidine and its derivatives, which were pharmacologically tested in 1958.
1: The experimental experiment of the failure of the chemical structure of benzene ring liding showed that benzene ring-lying had anaesthetic effect on rodents, which would cause pigeons to fall into a coma.
surprised the researchers with the anaesthetic effects of benzene cyclobenzene, and then allowed an assistant researcher named Edward F. Domino to further expand the experiment.
Domino's found that benzene ring is bound to cause delirium adverse reactions in dogs, but it is an extraordinary anaesthetic for monkeys and is safe.
In animal trials, Parke Davis decided to use benzene ring profit for clinical surgery, but the results were less than expected, in patients given benzene ring profit, there are serious deliriums and hallucinations, long-term use will make people addicted, excessive use will make people unconscious, some people will appear epilepsy and suicide behavior, this phenomenon is unacceptable.
At the same time, a psychologist named Elliott Luby was also interested in benzene ringing, which he had given to schizophrenics and found to be more aggressive and difficult to manage, which seemed to aggravate the condition.
research is still ongoing, but a few years later, there is a consensus that benzene ring is not suitable for use as an anaesthetic.
The successful arrival of Parke Davis did not eventually give up such research, benzene ring profit although there will be delirium phenomenon, but if the synthesis of short-acting benzene cyclolyceride derivatives, will only allow patients to appear delirium in a short period of time, like ether anesthesia, may be accepted by patients, so they went on to look for new benzene ring delirium derivatives.
1962, a chemistry doctor named Calvin Lee Stevens synthesized a variety of structurally unique derivatives and delivered them to pharmacologists for animal experiments, mainly in monkeys.
so-called emperors, they found an excellent anesthetic and a short-acting, high-security compound named CI-581, later ketamine.
trial of ketamine in 1964 and was approved by the FDA in 1970 as a short-acting desolation anaesthetic.
ketamine anesthesia is slightly less effective than benzene, but it has a shorter duration of effect, making patients less likely to experience side effects.
2: The chemical structure of ketamine "fog" ketamine, although on the market, but for a long time still do not know the target of action.
until 1982, David Lodge discovered that its target was the NMDA subject (Glutamate N Methyl-D-aspartate calcium channel).
ketamine has been shown to act competitively on NMDA subjects, inhibiting NMDA subjects to reduce neuronal activity and produce anesthesia.
claim was later confirmed by several scientists.
addition, the scientists also found that (S)-(-) - ketamine is twice as active as the anti-cyclone, and ketamine metabolites are also very active.
"evil" angel during the Vietnam War, the anti-war sentiment in the United States is strong, the war to the United States soldiers and veterans brought physical and mental harm.
During this period, benzodialycen and ketamine, which are anaesthetic agents, were used extensively in the wounded because they not only had an anesthetic analgesic effects, but also had various side effects that caused the wounded to develop hallucinations and pleasures that seemed like the soul was detached from the body, making them very popular in the United States.
But after a lot of ketamine use, the consequences are terrible, poisoning occurs frequently, but also can cause the user's mood instability, make them feel anxious and depressed, and eventually tired of the world and choose suicide.
ketamine devours people's health like a tiger.
later, the Government became aware of the seriousness of the problem and classified benzene as a Class I controlled drug and ketamine as a Class III controlled drug.
Figure 3: Ketamine is as ferocious as a tiger, taking people's lives analgesic effects After several studies have shown that ketamine not only act on NMDA subjects, but also on a depolarized cation channel (HCN) in the cerebral cortical layer; The separation of the limbic system from the hyaluralurome-neo-cortical system creates a unique state of anesthesia, manifested in woody rigidity, sedation, forgetting and significant analgesia, known as "separation anesthesia";
, ketamine has been used in a variety of pain treatment, such as postoperative pain, advanced cancer pain and so on.
antidepressant effects as early as 2000, Berman et al. first found that ketamine has good therapeutic effects in patients with depression.
In 2006, a NIH clinical study of patients with refractic depression in the United States had similar results, with a single intravenous sub-anaesthetic dose of ketamine, which quickly produced significant antidepressant effects and sustained a week of treatment.
March 5, 2019, the FDA approved Janssen's SPRAVATO™ (esketamine, S-form ketamine) CIII nasal spray for the treatment of adults with immune depression.
ketamine, which is used as an anaesthetic, has been used clinically because of its significant anaesthetic effect, but is strictly controlled because of its hallucinogenic and coma-inducing consequences.
scientists have never given up ketamine, has been studying its application in new areas, the so-called Phoenix Nirvana, bath fire reborn, people found its antidepressant effect, which is also a major breakthrough in the field of antidepressants.
that ketamine is a "double-sided angel" is not too much, but how to use it, it is still in the heart.
: 1. History of anaesthesia:The ketamine story – past, present and future.2.Ketamine: Teaching an Old DrugNew Tricks.3.Taming the Ketamine Tiger.4.Ketamine: New Indications for an Old Drug.5.