Topic
Ethylmorphine
About: Ethylmorphine is a research topic. Over the lifetime, 307 publications have been published within this topic receiving 8077 citations. The topic is also known as: Dionine & Ethyl morphine.
Papers published on a yearly basis
Papers
Journal Article•
TL;DR: The N-demethylating enzyme is proposed as a model for the study of narcotic-drug receptor sites and the degree of tolerance, cross-tolerance and depression of enzymatic activity depends on the amount of drug given per day rather than on the duration of drug administration.
Abstract: Chronic administration of morphine and morphine-nalorphine mixtures to the rat results in a profound diminution of the analgesic response to a test close of morphine (tolerance) and a profound reduction in the ability of liver enzyme preparations from these animals to N-dealkylate morphine and nalorphine.
Moderate reduction of the analgesic response to a test dose of morphine (cross-tolerance) and moderate reduction of N-demethylation of morphine by liver enzyme preparations from rats occur when nalorphine and normorphine are given chronically. The in vitro N-dealkylation of nalorphine is not affected significantly. More than one enzyme seems to be involved in the N-dealkylation of narcotic drugs. The degree of tolerance, cross-tolerance and depression of enzymatic activity depends on the amount of drug given per day rather than on the duration of drug administration.
Based on the observed parallelism of depression of enzyme activity and of analgesic response, the N-demethylating enzyme is proposed as a model for the study of narcotic-drug receptor sites.
747 citations
TL;DR: It is concluded that, in addition to glucocorticoids, macrolide antibiotics are specific inducers of P-450p.
Abstract: We administered triacetyloleandomycin (TAO) to rats and found that this macrolide antibiotic is the most efficacious inducer of liver microsomal cytochrome P-450 (P-450) examined to date. Liver microsomes prepared from TAO-treated rats contained greater than 5.0 nmol of P-450/mg of protein and a single induced protein as judged by analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This protein comigrated with P-450p, the major form of P-450 induced in liver microsomes of rats treated with pregnenolone-16 alpha-carbonitrile (PCN) or dexamethasone (DEX). On immunoblots of such gels developed with antibodies to P-450p, the TAO-induced protein reacted strongly as a single band. There was strict parallelism between the amount of immunoreactive P-450p in liver microsomes prepared from untreated rats or from rats treated with phenobarbital, TAO, DEX, or PCN, the ability of these microsomes to catalyze conversion of TAO to a metabolite which forms a spectral complex, and the ethylmorphine and erythromycin demethylase activities. Antibodies to P-450p specifically blocked microsomal TAO metabolite complex formation and ethylmorphine and erythromycin demethylase activities. Moreover, anti-P-450p antibodies completely immunoprecipitated solubilized TAO metabolite complexes prepared by detergent treatment of liver microsomes obtained from TAO-treated rats. Finally, we found that the major form of P-450 isolated from liver microsomes of TAO-treated rats and purified to homogeneity was indistinguishable from purified P-450p as judged by molecular weights, spectral characteristics, enzymatic activities, ability to bind TAO, peptide maps, and amino-terminal amino acid sequences. We concluded that, in addition to glucocorticoids, macrolide antibiotics are specific inducers of P-450p.
317 citations
TL;DR: Many opioids may exert their pharmacological actions predominantly through metabolites, and analgesics with high clinical potency containing a methoxyl group at position 3 had relatively weak receptor binding, whilst their O-demethylated metabolites had much stronger binding.
260 citations
Journal Article•
TL;DR: Kinetic evidence is presented to support the view that the activity of SKF 525-A may be due in part to one or more of its metabolites, and it is suggested that many of these compounds produce their inhibitory effects by serving as alternative substrates.
Abstract: SKF 525-A and ten congeners were incubated with hepatic microsomes, and all were found to be N-dealkylated. The kinetics of the inhibition of the N-demethylation of ethylmorphine by the eleven compounds was studied and found to be competitive in all cases. These results strongly suggest that SKF 525-A type compounds produce their effects by combining with the active site of time N-demethylase, not by altering the permeability of the lipoid membrane of the microsomime or by uncoupling an oxidative mechanism as has been postulated by others. Kinetic data were presented which indicated that many of these compounds produce their inhibitory effects by serving as alternative substrates. Kinetic evidence is also presented to support the view that the activity of SKF 525-A may be due in part to one or more of its metabolites.
202 citations
TL;DR: Pretreatment of female rats with pregnenolone-16α-carbonitrile (PCN) for 212 days resulted in a significant increase in cytochrome P-450 content and NADPH-cytochrome c reductase activity in hepatic microsomes, and studies on the induction of enzymes that metabolize the above three substrates revealed that PB, PCN, and 3-MC exerted their greatest stimulatory effect on benzphetamine N-demethylation,
187 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2022 | 2 |
| 2021 | 2 |
| 2020 | 3 |
| 2015 | 1 |
| 2014 | 1 |
| 2012 | 1 |