57-42-1

Usage

Uses

Used in Pharmaceutical Industry:
Meperidine is used as an analgesic for the management of moderate to severe pain. Its quick onset of action and ability to penetrate the blood-brain barrier make it an effective pain reliever. However, due to its potential for abuse and the availability of alternative medications with lower abuse potential, its use has declined in recent years.
Used in Research and Development:
Meperidine serves as a starting point for the development of new, more potent, and safer analgesic agents. Researchers can study its structure and mechanism of action to design new drugs with improved properties and reduced side effects or abuse potential.
Used in Veterinary Medicine:
Meperidine is also used in veterinary medicine as an analgesic for the management of pain in animals. Its effectiveness in providing pain relief and its quick onset of action make it a valuable tool in veterinary practice.

Therapeutic Function

Narcotic analgesic

Biological Functions

Meperidine (Demerol) is a phenylpiperidine derivative of morphine that was developed in the late 1930s as a potential anticholinergic agent. It has some anticholinergic side effects that lead to tachycardia, blurred vision, and dry mouth. Meperidine is approximately onefifth as potent as morphine and is absorbed only half as well when administered orally as parenterally. It has a rapid onset and short duration of action (2 hours), that is, approximately one-fourth that of morphine. Like morphine, meperidine has an active metabolite, normeperidine, formed by N-demethylation of meperidine. Normeperidine is not analgesic but is a proconvulsant and a hallucinogenic agent. For this reason, meperidine use in patients with renal or liver insufficiency is contraindicated because of the decreased clearance of the drug and its metabolite. Convulsant activity has been documented in elderly patients given meperidine and in patients using PCA who have decreased renal function. Meperidine differs from morphine in that it has far less antitussive effect and little constipative effect. The drug is particularly useful in cancer patients and in pulmonary patients, in whom the cough reflex must remain intact. However, it does have more seizure-inducing activity than morphine. Although meperidine produces spasms of the biliary tract and colon, such spasms are of shorter duration than those produced by morphine. Meperidine readily passes the placenta into the fetus. However, respiratory depression in the newborn has not been observed, and meperidine clearance in the newborn is rapid in that it does not rely upon conjugation to glucuronides. Meperidine, unlike morphine, has not been associated with prolongation of labor; conversely, it increases uterine contractions.

Precautions

Contraindications are similar to those of morphine. In addition, because normeperidine accumulates in renal dysfunction and meperidine accumulates in hepatic dysfunction, meperidine is contraindicated in such patients because of convulsant effects. Similarly, the use of meperidine is contraindicated in patients who have a history of seizures or who are taking medication to prevent seizures. Phenytoin administered for seizures may reduce the effectiveness of meperidine by increasing the metabolism of the drug in the liver. Meperidine is not generally used in patients with cardiac dysfunction, since its anticholinergic effects can increase both heart rate and ectopic beats.

InChI:InChI=1/C15H21NO2/c1-3-18-14(17)15(9-11-16(2)12-10-15)13-7-5-4-6-8-13/h4-8H,3,9-12H2,1-2H3

Upstream product

• 3627-62-1 1-methyl-4-phenyl-piperidine-4-carbonitrile 
• 3627-48-3 pethidinic acid 
• 50-00-0 formaldehyd 
• 77-17-8 Normeperidine 
• 74-88-4 methyl iodide 
• 64-17-5 ethanol 
• 107054-93-3 (4-chloro-1-methyl-[4]piperidyl)-phenyl ketone 
• 51-75-2 nitrogen mustard 
• 71258-18-9 1-benzyl-4-phenyl-piperidine-4-carbonitrile; hydrochloride 
• 40481-13-8 4-phenyl-4-cyanopiperidine 
• 723272-14-8 4-bromo-2-(2-bromo-ethyl)-2-phenyl-butyric acid 
• 140-29-4 phenylacetonitrile 
• 92039-99-1 (1-methyl-[4]piperidyl)-phenyl ketone; hydrochloride 
• 854432-10-3 4-bromo-2-(2-bromo-ethyl)-2-phenyl-butyric acid ethyl ester 

Downstream Products

• 124120-06-5 4,4'-bis-ethoxycarbonyl-1,1'-dimethyl-4,4'-diphenyl-1,1'-butanediyl-bis-piperidinium; dibromide 
• 120174-91-6 4,4'-bis-ethoxycarbonyl-1,1'-dimethyl-4,4'-diphenyl-1,1'-pentanediyl-bis-piperidinium; dibromide 
• 4220-07-9 4-ethoxycarbonyl-1,1-dimethyl-4-phenyl-piperidinium; iodide 
• 4220-10-4 (1-methyl-4-phenyl-piperidin-4-yl)-methanol 
• 101107-74-8 4-cyclohexyl-1-methyl-piperidine-4-carboxylic acid ethyl ester 
• 13147-07-4 meperidine N-oxide 
• 3627-45-0 4-phenyl-piperidine-4-carboxylic acid 
• 3627-48-3 pethidinic acid 
• 77-17-8 Normeperidine 
• 4220-06-8 p-hydroxymeperidine 
• 3691-79-0 1-methyl-4-phenyl-piperidine-4-carbaldehyde 
• 50-13-5 meperidine hydrochloride 
• 117878-08-7 4-[2-(1,1-dimethyl-4-phenyl-piperidinium-4-ylmethoxy)-ethyl]-4-methyl-morpholinium; diiodide 
• 111416-94-5 1,1-dimethyl-4-phenyl-4-(2-trimethylammonio-ethoxymethyl)-piperidinium; diiodide 

Relevant academic research and scientific papers

Muscarinic acetylcholine receptor binding affinities of pethidine analogs

A series of pethidine analogs were synthesized and their affinities for the [3H]N-methyl-scopolamine (NMS) binding site on muscarinic acetylcholine receptors (mAChRs) were determined using M1, M3 or M5 human mAChRs expressed by Chinese hamster ovary (CHO) cell membranes. Compound 6b showed the highest binding affinities at M1, M3 and M5 mAChRs (Ki = 0.67, 0.37, and 0.38 μM, respectively).

PHENYLPIPERIDINE MODULATORS OF MU-OPIOID RECEPTOR

The present invention relates to new phenylpiperidine modulators of μ-opioid receptors, pharmaceutical compositions thereof, and methods of use thereof.

Opioids and efflux transporters. Part 3: P-glycoprotein substrate activity of 3-hydroxyl addition to meperidine analogs

Numerous studies have shown that many clinically employed opioid analgesics are substrates for P-glycoprotein (P-gp), suggesting that up-regulation of P-gp may contribute to the development of central tolerance to opioids. The studies herein focus on the development of SAR for P-gp substrate activity in the meperidine series of opioids. Addition of a 3-OH to meperidine and the ketone analog of meperidine yielding bemidone and ketobemidone, respectively, significantly increased P-gp substrate affinity. The results of this study have implications in the development of novel analgesics to be utilized as tools to study the contribution of P-gp on the development of central tolerance to opioids.

Opioids and efflux transporters. Part 1: P-Glycoprotein substrate activity of N-substituted analogs of meperidine

P-Glycoprotein (P-gp) is an efflux transporter which is up-regulated at the blood-brain barrier in both morphine- and oxycodone-tolerant rats. Numerous studies have shown that many clinically employed opioid analgesics are substrates for P-gp, suggesting that up-regulation of P-gp may contribute to the development of central tolerance to opioids. The studies herein focus on the development of SAR for P-gp substrate activity in the meperidine series of compounds, and show that a meperidine analog of greater potency, N-phenylbutyl-N-normeperidine, has low activity as a P-gp substrate and has the potential to be utilized as a tool to study the contribution of P-gp to the development of central tolerance to opioids.

Process for preparing N,N-bis(2-hydroxyethyl)benzylamine and N,N-bis(2-chloroethyl)benzylamine

Improvements are shown in the successive preparations of N,N-bis(2-hydroxyethyl)benzylamine starting with benzyl chloride, its conversion to the corresponding N,N-bis(2-chloroethyl)benzylamine in substantially quantitative yield in toluene solution and using the latter by reaction with phenylacetonitrile in the presence of aqueous sodium hydroxide solution and a tetra-n-butylammonium salt, preferably the hydrogen sulfate, to produce improved over-all yields of up to over 75% (based on benzyl chloride) of 1-benzyl-4-cyano-4-phenylpiperidine hydrochloride, an intermediate for preparing meperidine.

ADDITION OF CARBON NUCLEOPHILES TO ARENE-CHROMIUM COMPLEXES

The electrophilic reactivity of arenes coordinated to the chromium tricarbonyl unit has been developed into several distinct methods for coupling carbon nucleophiles with aromatic rings.Addition of the nucleophile produces stable η-cyclohexadienyl chromium complexes which can be oxidized to induce loss of the endo hydrogen and the metal, overall nucleophilic substitution for hydrogen.Alternatively, the intermediate can be protonated and the resulting cyclohexa-1,3-diene can be detached from the chromium, effecting nucleophilic addition with reduction of one double bond.If a halogen (F, Cl) is present as a ring substituent, and if the nucleophile can migrate about the arene ligand, then loss of halide can occur parallel with classical nucleophilic aromatic substitution for halogen in electron-deficient haloarenes.With substituted arenes, the regioselectivity of addition becomes important and is often very high.Particularly useful are strong resonance donor substituents (RO-, R2N-, F-) where selectivity for meta attack is high.Indole provides an excellent example of selective activation, as the six-membered ring complexes selectively and is then susceptible to nucleophilic substitution, predominantly at the 4 and 7 positions.Substitution for halogen is a somewhat limited process and depends upon the nature of the nucleophile.Very reactive nucleophiles add to unsubstituted positions and are often slow to isomerize to the ipso position from which loss of halide can occur.