Phenoperidine

Phenoperidine

Systematic (IUPAC) name
ethyl 1-(3-hydroxy-3-phenylpropyl)-4-phenylpiperidine-4-carboxylate
Clinical data
Legal status	AU: S8 (Controlled) DE: Anlage I (Controlled) US: Schedule I
Routes of administration	Intravenous
Pharmacokinetic data
Metabolism	Liver
Excretion	Bile and Urine
Identifiers
CAS Number	562-26-5 N
ATC code	N01AH04 (WHO)
PubChem	CID: 11226
ChemSpider	10752 Y
UNII	G9BH09J4JW Y
KEGG	D02611 Y
Chemical data
Formula	C23H29NO3
Molecular mass	367.481
SMILES OC(C1=CC=CC=C1)CCN(CC2)CCC2(C3=CC=CC=C3)OC(CC)=O
InChI InChI=1S/C23H29NO3/c1-2-27-22(26)23(20-11-7-4-8-12-20)14-17-24(18-15-23)16-13-21(25)19-9-5-3-6-10-19/h3-12,21,25H,2,13-18H2,1H3 Y Key:IPOPQVVNCFQFRK-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Phenoperidine (Operidine or Lealgin), is an opioid used as a general anesthetic.

Medical use

Phenoperidine is an opioid pain killer -- narcotic analgesic.

Pharmacology

It is a derivative of isonipecotic acid, like pethidine, and is metabolized in part to norpethidine. It is 20-200 times as potent as pethidine as an analgesic. 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, of the company now known as Janssen Pharmaceutica, who was seeking better opioid pain-killers. His two prototype drugs were methadone and pethidine, each which had been invented in 1930s by Otto Eisleb, who worked for IG Farben. His initial work starting with methadone yielded dextromoramide 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 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, as well as diphenoxylate, which lacked the opioid's analgesic properties but still stopped peristalsis 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 in 1960, which proved to be ten times more potent than phenoperidine.

Historical Uses

In 1959, the combination of phenoperidine and haloperidol was first used in Europe in anesthesia 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 and droperidol, 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 Convention for Limiting the Manufacture and Regulating the Distribution of Narcotic Drugs by the World Health Organization via the Single Convention on Narcotic Drugs.

In the US it is classified as a schedule 1 opiate and is categorized as a Drug Enforcement Administration (DEA) controlled substance with a corresponding code 9641.