Phenoperidine(Operidine or Lealgin), is an
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
analgesic
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
which is structurally related to
pethidine
Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a synthetic opioid analgesic, pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemis ...
and is used clinically as a
general anesthetic
General anaesthetics (or anesthetics, see spelling differences) are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma ...
.
Medical use
Phenoperidine is an
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
pain killer --
narcotic analgesic
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
.
Pharmacology
It is a derivative of
isonipecotic acid, like
pethidine
Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a synthetic opioid analgesic, pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemis ...
, and is metabolized in part to
norpethidine
Norpethidine (normeperidine, pethidine intermediate B) is a 4-phenylpiperidine derivative that is both a precursor to, and the toxic metabolite of, pethidine (meperidine). It is scheduled by UN Single Convention on Narcotic Drugs. It is a Sched ...
. Its potency range is due to method of ingestion. figure 20-80 times as potent as pethidine as an
analgesic
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It ...
. The greatly increased potency essentially eliminates the toxic effects of norpethidine accumulation which are seen when pethidine is administered in high doses or for long periods of time.
History and Synthesis
Phenoperidine was first synthesized in 1957 by
Paul Janssen
Paul Adriaan Jan, Baron Janssen (12 September 1926 - 11 November 2003) was a Belgian physician. He was the founder of Janssen Pharmaceutica, a pharmaceutical company with over 20,000 employees which is now a subsidiary of Johnson & Johnson.
Ea ...
, of the company now known as
Janssen Pharmaceutica
Janssen Pharmaceuticals is a pharmaceutical company headquartered in Beerse, Belgium, and wholly-owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen.
In 1961, Janssen Pharmaceuticals was purchased by New Jersey-based American c ...
, who was seeking better
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
pain-killers.
His two prototype drugs were
methadone
Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroin ...
and
pethidine
Pethidine, also known as meperidine and sold under the brand name Demerol among others, is a synthetic opioid analgesic, pain medication of the phenylpiperidine class. Synthesized in 1938 as a potential anticholinergic agent by the German chemis ...
, each which had been invented in 1930s by Otto Eisleb, who worked for
IG Farben
Interessengemeinschaft Farbenindustrie AG (), commonly known as IG Farben (German for 'IG Dyestuffs'), was a German chemical and pharmaceutical conglomerate (company), conglomerate. Formed in 1925 from a merger of six chemical companies—BASF, ...
. His initial work starting with methadone yielded
dextromoramide
Dextromoramide (Palfium, Palphium, Jetrium, Dimorlin) is a powerful opioid analgesic approximately three times more potent than morphine but shorter acting. It is subject to drug prohibition regimes, both internationally through UN treaties and b ...
in 1954. Janssen then turned to making pethidine analogues, due in part to the less complicated chemistry of the compound. During his explorations, he replaced the methyl group attached to the pethidine nitrogen with a
propiophenone
Propiophenone (shorthand: benzoylethane or BzEt) is an aryl ketone. It is a colorless, sweet-smelling liquid that is insoluble in water, but miscible with organic solvents. It is used in the preparation of other compounds.
Production
Propiophenon ...
group, and this yielded phenoperidine, in 1957. Phenoperidine was determined to have decreased stability and enhanced lipophilicity compared to pethidine. Soon after, studies in mice showed that phenoperidine was over 100 times more potent than pethidine.
[
In 1958, the same line of work yielded “one of the greatest advances of the 20th century psychiatry", ]haloperidol
Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...
,[ as well as ]diphenoxylate
Diphenoxylate is a centrally active opioid drug of the phenylpiperidine series that is used as a combination drug with atropine for the treatment of diarrhea. Diphenoxylate is an opioid and acts by slowing intestinal contractions; the atropine i ...
, which lacked the opioid's analgesic properties but still stopped peristalsis
Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, which ...
in the intestines, a typical side effect of opioids; Janssen brought diphenoxylate to market as a drug to treat diarrhea. And through further advances, Janssen created fentanyl
Fentanyl, also spelled fentanil, is a very potent synthetic opioid used as a pain medication. Together with other drugs, fentanyl is used for anesthesia. It is also used illicitly as a recreational drug, sometimes mixed with heroin, cocaine ...
in 1960, which proved to be ten times more potent than phenoperidine.
Historical Uses
In 1959, the combination of phenoperidine and haloperidol
Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...
was first used in Europe in anesthesia
Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...
to induce a detached, pain free state called Neuroleptic analgesia; the use of that mixture boomed in early 1960s but was overtaken by the combination of fentanyl
Fentanyl, also spelled fentanil, is a very potent synthetic opioid used as a pain medication. Together with other drugs, fentanyl is used for anesthesia. It is also used illicitly as a recreational drug, sometimes mixed with heroin, cocaine ...
and droperidol
Droperidol (Inapsine, Droleptan, Dridol, Xomolix, Innovar ombination with fentanyl">fentanyl.html" ;"title="ombination with fentanyl">ombination with fentanyl is an antidopaminergic medication, drug used as an antiemetic (that is, to prevent o ...
, which was widely used through the 1980s. These combination approaches were not adopted in the US.
Regulations
In 1961 phenoperidine was added to the 1931 by the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
via the Single Convention on Narcotic Drugs
The Single Convention on Narcotic Drugs, 1961 (Single Convention, 1961 Convention, or C61) is an international treaty that controls activities (cultivation, production, supply, trade, transport) of specific narcotic drugs and lays down a syst ...
.[WHO Executive Board. 17 April 196]
Action in Respect of the International Convention on Narcotic Drugs.
/ref>
In the US it is classified as a schedule 1 opiate and is categorized as a Drug Enforcement Administration
The Drug Enforcement Administration (DEA; ) is a Federal law enforcement in the United States, United States federal law enforcement agency under the U.S. Department of Justice tasked with combating drug trafficking and distribution within th ...
(DEA) controlled substance with a corresponding code 9641.
References
Further reading
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{{Opioidergics
General anesthetics
4-Phenylpiperidines
Secondary alcohols
Carboxylate esters
Mu-opioid receptor agonists
Ethyl esters