57-42-1

Basic information

• Product Name: MEPERIDINE
• Synonyms: MEPERIDINE;1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester;1-methyl-4-phenyl-4-piperidinecarboxylicacidethylester;1-methyl-4-phenyl-4-piperidinecarboxylicaciethylester;1-Methyl-4-phenylisonipecotic acid, ethyl ester;1-methyl-4-phenylisonipecoticacid,ethylester;1-methyl-4-phenylisonipecoticacidethylester;1-methyl-4-phenyl-isonipecoticaciethylester
• CAS NO: 57-42-1
• Molecular Formula: C₁₅H₂₁NO₂
• Molecular Weight: 247.33
• EINECS: 200-329-1
• Product Categories: Controlled Drug StandardsAlphabetic;M;MEA - MES;Stable Isotopes
• Mol File: 57-42-1.mol
• Article Data: 7

Chemical Properties

• Melting Point: 270°C
• Boiling Point: 390.37°C (rough estimate)
• Flash Point: 11 °C
• Appearance: /
• Density: 1.0267 (rough estimate)
• Refractive Index: 1.5130 (estimate)
• Storage Temp.: −20°C
• PKA: pKa 8.7 (Uncertain)
• Water Solubility: 6.55g/L(25 oC)
• CAS DataBase Reference: MEPERIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: MEPERIDINE(57-42-1)
• EPA Substance Registry System: MEPERIDINE(57-42-1)

Safety Data

• Hazard Codes: F,T
• Statements: 11-23/24/25-39/23/24/25
• Safety Statements: 7-16-36/37-45
• RIDADR: UN 1230 3/PG 2
• WGK Germany: 1
• Hazardous Substances Data: 57-42-1(Hazardous Substances Data)

Usage

Uses

Analgesic (narcotic).

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.

General Description

Meperidine (Demerol) was discovered in 1939 during a serendipitous screening of compounds being studied for antispasmodic activity. Mice given meperidine were noted to carry their tails in an erect position (the Straub tail reaction), which was indicative of narcotic analgesia. This led to the study of meperidine and derivatives as analgesic agents. Meperidine was found to have low potency at the receptor compared with morphine (0.2%) but much higher penetration into the brain resulting in a compound with about 10% of the potency of morphine.Structural changes that increase the potency of meperidine include the introduction of an mhydroxyl on the phenyl ring, substituting the methyl on the N for a phenylethyl or a p-aminophenylethyl. Replacing the N-methyl with an N-allyl or N-cyclopropylmethyl group does not generate an antagonist, unlike the similar substitution of the morphine congeners. Meperidine quickly penetrates the blood-brain barrier and thus has a quick onset of activity and a high abuse potential.

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 
• 51-75-2 nitrogen mustard 
• 64-17-5 ethanol 
• 3627-48-3 pethidinic acid 
• 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 
• 107054-93-3 (4-chloro-1-methyl-[4]piperidyl)-phenyl ketone 
• 854432-10-3 4-bromo-2-(2-bromo-ethyl)-2-phenyl-butyric acid ethyl ester 
• 74-89-5 methylamine 
• 77-17-8 Normeperidine 
• 74-88-4 methyl iodide 

Downstream Products

• 50-13-5 meperidine hydrochloride 
• 3691-79-0 1-methyl-4-phenyl-piperidine-4-carbaldehyde 
• 4220-10-4 (1-methyl-4-phenyl-piperidin-4-yl)-methanol 
• 3627-45-0 4-phenyl-piperidine-4-carboxylic acid 
• 3627-48-3 pethidinic acid 
• 77-17-8 Normeperidine 
• 13147-07-4 meperidine N-oxide 
• 4220-06-8 p-hydroxymeperidine 
• 101107-74-8 4-cyclohexyl-1-methyl-piperidine-4-carboxylic acid ethyl ester 
• 4220-07-9 4-ethoxycarbonyl-1,1-dimethyl-4-phenyl-piperidinium; iodide 
• 120174-91-6 4,4'-bis-ethoxycarbonyl-1,1'-dimethyl-4,4'-diphenyl-1,1'-pentanediyl-bis-piperidinium; dibromide 
• 124120-06-5 4,4'-bis-ethoxycarbonyl-1,1'-dimethyl-4,4'-diphenyl-1,1'-butanediyl-bis-piperidinium; dibromide 
• 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 articles and documents

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).

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.

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.