6-ethylmorphine

Ethylmorphine hydrochloride (Dionine ) resembles codeine more closely in its action than it does morphine. It is used primarily as a chemotic to produce vasodilatation and edema of the conjunctiva in corneal ulcer and other inflammatory conditions of the eye. For this purpose, it is instilled topically as a 1 to 5% solution in the eye. It has also been used as an antitussive in doses of 15 mg. 

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The use of selective P-antagonists for treatment of CHF has included the P -blocker metoprolol (Table 1) and results of clinical trials suggest long-term beneficial effects. Selective P -antagonists have also been tested, an example of which is xamoterol [81801 -12-9], C2 H25N20, which is (i)-A/-(2-hydroxy-3-(4-hydroxyphenoxy)propylamino)ethylmorphine-4-carboxamide. Xamoterol exhibits approximately 50% of the activity of isoproterenol, and serves to provide modest inotropic effects (128,129). 

The processes used in the manufacture of morphine are believed to be still based on that described by the Scottish chemist Gregory,in 1833, with improvements devised by Anderson. A description has been published by Schwyzer, who also deals with the manufactme of codeine, narcotine, cotarnine, and the commercially important morphine derivatives, diamorphine (diacetylmorphine), and ethylmorphine (morphine ethyl ether). More recently Barbier has given an account of processes, based on long experience in the preparation of alkaloids from opium. Kanewskaja has described a process for morphine, narcotine, codeine, thebaine and papaverine, and the same bases are dealt with by Chemnitius, with the addition of narceine, by Busse and Busse, and by Dott. It is of interest to note that a number of processes for the extraction and separation of opium alkaloids have been protected by patent in Soviet Russia. ... 

A number of homologues of codeine have been prepared by the alkylation of morphine for example, ethylmorphine, which is used in medicine... 

Codeine (morphine methyl ether) resembles morphine in its general effect, but is less toxic and its depressant action less marked and less prolonged, whilst its stimulating action involves not only the spinal cord, but also the lower parts of the brain. In small doses in man it induces sleep, which is not so deep as that caused by morphine, and in large doses it causes restlessness and increased reflex excitability rather than sleep. The respiration is slowed less than by morphine (cf. table, p. 261). Cases of addiction for codeine can occur but according to Wolff they are rare. The best known ethers of morphine are ethylmorphine and benzyl-morphine [cf., table, p. 261), both used to replace morphine or codeine for special purposes. 

C 7H,7N03 57-27-2) see Apomorphine Codeine Ethylmorphine Hydromorphone Nalorphine Pholcodine... 

For instance morphine (1) can be detected by the formation of various quinones via apomorphine as intermediate [4, 12, 13]. All morphines with an OH group in the 6-position and a double bond (codeine, ethylmorphine etc.) first undergo an acid-catalyzed rearrangement according to the following scheme [12] ... 

In the case of heroin, the indicator used is nonexclusive of heroin consumption, as it is also excreted to a high extent after administration of therapeutic morphine and in minor proportions after use of other opioids, such as codeine, pholcodine, and ethylmorphine. In order to obtain comparable results to previous studies [25, 31], an average medical administration of morphine of 10 mg/capita/year [45] and an excretion rate of 85% of morphine after therapeutic use [25, 31] were considered in the calculations. 

Disulfoton induced the liver MFO system in animals (Stevens et al. 1973). In the same study, exposure to disulfoton orally for 3 days also increased ethylmorphine N-demethylase and NADPH oxidase activities, but had no effect on NADPH cytochrome c reductase. Thus, the induction of the MFO system required repeated dosing with relatively high doses. Furthermore, these changes are not specific for disulfoton exposure, and these subtle liver effects require invasive techniques in humans to obtain liver tissue for performance of these enzyme assays. 

Pretreatment with the Type I substrate, ethylmorphine, resulted in 100% mortality in both rats and mice, and aminopyrine pretreatment resulted in 100% and 64% mortality in rats and mice, respectively, exposed to disulfoton (Pawar and Fawade 1978). Nickel chloride, cobalt chloride, or cycloheximide decreased the levels of cytochrome bs, cytochrome c reductase, and total heme in rats (Fawade and Pawar 1983). These electron transport components were further decreased in rats pretreated with these inhibitors and given a single dose of disulfoton. Data from this study suggests an additive effect, since disulfoton also decreases the activities of these components. Evidence of an additive effect between disulfoton and these metabolic inhibitors was suggested by the decrease in ethylmorphine N-demethylase and acetanilide hydroxylase activities when rats were given an inhibitor followed by disulfoton. In another experiment, these inhibitors decreased the activity of delta-aminolevulinic acid synthetase, but this decrease was reversed when disulfoton was administered. 

Arylhydrocarbon (benzo[a]pyrene) hydroxylase, benzphetamine-N-demethylation, ethylmorphine-N-demethylation, ethoxycoumarin-0-deethylation and ethoxyresorufin-0-deethylation were performed by published procedures (31,32,33,34), but optimized for use with trout microsomes as described previously (30, 35). Hemoprotein P-450 was determined by the procedure of Estabrook et al. (36) to avoid spectral interference by hemoglobin. Microsomal protein content was estimated either by the method of Ross and Shatz (37) or Lowry et al. (38), using bovine serum albumin standards. 

Ethylmorphine and benzphetamine are N-demethylated specifically by rodent cytochrome(s) P-450 (as opposed to cytochrome(s) P] -450) in the rat phenobarbital and the polyhalogenated biphenyls induce these demethylation reactions. However, it is clear that no such stimulation occurred in the rainbow trout (Table II). 

Anders, M.W. and Mannering, G.J. Kinetics of the inhibition of the N-demethylation of ethylmorphine by 2-diethylamino-ethyl 2,2-diphenyl valerate HC1 (SKF-525A) and related compounds. Mol. Pharmacol. (1966) 2 319-327. 

Antiarrhythmics encainide, flecainide, mexiletine Beta-blockers alprenolol, metoprolol, propranolol, timolol Opiates codeine, dextromethorphan, ethylmorphine... 

Ethacrinic acid, 120 Ethambutol, 222 Ether cleavage, 314, 368 Ethionamide, 255 Ethisterone, 163, 172 Ethithiazide, 358 Ethoheptazine, 303 Ethopropazine, 373 Ethosuximide, 228 Ethotoin, 245 Ethoxysolamide, 327 Ethylestrenol, 170 Ethylmorphine, 287 Ethynodiol diacetate, 165, 186 Ethynodrel, 164 Ethynylestradiol, 162 Etonitazine, 325... 

G6. Gram, T. E., Guarino, A. M., Schroeder, D. H., and Gillette, J. R., Changes in certain kinetic properties of hepatic microsomal hydroxylase and ethylmorphine demethylase associated with postnatal development and maturation in male rats. Biochem. J. 113, 681-685 (1969). 

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