Morphine ethylmorphine

V-Dealkylation RMHCH3 RNHj + CH20 Morphine, ethylmorphine, benzphetamine, aminopyrine, caffeine, theophylline... 

Theodoridis, G. Papadoyannis, I. Vasilikiotis, G. Tsoukali-Papadopoulou, H. Reversed-phase high-performance liquid chromatography-photodiode-array analysis of alkaloid drugs of forensic interest. J.Chromatogr.B, 1995, 668, 253-263 [also amphetamine, bamifylline, caffeine, cocaine, codeine, dia-morphine, ethylmorphine, flufenamic acid, methadone, morphine, nalorphine, norcodeine, papaverine, quinine, scopolamine, strychnine, theobromine, theophylline, tolfenamic acid]... 

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. 

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. 

Opioid receptor binding Ethylmorphine is an ethyl congener of codeine and has a low opioid receptor affinity (Chen et al., 1991). Like codeine, it is metabolized to the active principle morphine. 

Pharmacokinetic properties Ethylmorphine (Aasmundstad et al., 1995) has a reasonable oral bioavailability. Like codeine, it is metabolized by O- and N-desalkylation, leading to nor-ethylmorphine, morphine, nor-morphine, and the respective glucuronides. 

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. 

Svensson JO, Andersson M, Gustavsson E, Beck O (2007) Electrospray LC-MS method with solid-phase extraction for accurate determination of morphine-, codeine-, and ethylmorphine-glucuronides and 6-acetylmorphine in urine. J Anal Toxicol 31(2) 81-86... 

The acetylation of morphine and of codeine by aspirin202 and the enzymatic hydrolysis of heroin203 and the reduction of codeinone204 have been studied. Dihydronorcodeine and dihydromorphine have been isolated from urine as metabolites of dihydrocodeine.205 Patents have been published covering the preparation of -(cyclopropylmethyOnormorphine,206 the conversion of thebaine into codeinone,207 and the preparation of nalorphine 6-sulphate.208 Salts of codeine and ethylmorphine with 5-carboxymethyl-2-thio-l,3-thiazan-4-one have been prepared.209 The circular dichroism210,211 and fluorescence characteristics212 of morphine and related bases have been studied. 

In this procedure, 120 to 200 mg of "white" hair, meaning hair not containing any opiates, pre-washed and reduced to a powder, are immersed into 20 mL of an aqueous solution containing 0.1 to 5 mg/L of codeine, ethylmorphine, 6-MAM, and morphine. This mixture is magnetically stirred for 5 h. 

The hair is then recovered by filtration and washed with 20 mL of HjO, followed by 20 mL of MeOH in order to eliminate the proportion of the drugs adsorbed by the hair surface. The concentrations of opiates in hair have been determined by GC/MS using the extraction method as described by Ahrens et al. The average soaking efficiency and standard deviations of soaking of 5 successive samples of soaked hair for codeine, ethylmorphine, 6-MAM, and morphine can be seen in Table 4. In addition, the levels of opiates in hair are directly proportional to the concentration of the soaking aqueous solution. Indeed, the graphical representation of the concentrations of opiates in the solution coupled with the same concentration in the hair follows a linear distribution (with correlation coefficients of 0.995 for codeine, 0.996 for ethylmorphine, 0.992 for 6-MAM, and 0.995 for morphine). ... 

The characterisation and quantification of opiates (morphine, 6-MAM, codeine, and ethylmorphine) are obtained with the aid of a GC/MS. The apparatus and the conditions used are the following ... 

Six 50-mg blank hair samples were extracted by SFE and the noise was integrated for the ion used for quantification (m/z = 355 for codeine, 369 for ethylmorphine, 383 for 6-MAM, and 397 for morphine) in a retention time window of tj + 0.5 min. The LOD and LOQ were determined (n = 6) using lUPAC methods. For each substance the standard deviation of the blank value (Sg) was determined. The mean area converted from the noise was calculated as concentration equivalent based on a calibration graph. The LOD is defined as 3Sg and the LOQ as lOSg. 

In these conditions, the detection limits are 30 pg/mg for codeine, ethylmorphine, and morphine, and 50 ppb for 6-MAM, while the quantification limits are 100 pg/mg for the first three opiates and 200 pg/mg for 6-MAM. These values are comparable to those obtained by Moeller et al., who proposed LODs of 100 pg/mg for opiates. 

Enzymatic digestion gives equally excellent results for the four opiates. Comparing this method with SFE shows that the two techniques are comparable for codeine and ethylmorphine, but show differences when it comes to 6-MAM and morphine. In fact the higher extraction yield for morphine and the lower yield for... 

The alkaloid contents of transformed and non-transformed calli were analyzed by an ELISA and an HPLC. The crude extract can be immediately subjected to the ELISA analysis as described above (sections 3.1, 3.4) using morphine-specific monoclonal antibody [145]. The morphine-specific antibody used has a high affinity for morphine, codeine, ethylmorphine, dihydromorphine, and dihydrocodeine, less reactivity with dihydromorphinone, dihydrocodeinone, and norcodeine, but almost no reactivity with naloxone and naltrexone [145]. 

NIH 5145) is a dithienyl compound, an opioid receptor AGONIST, with OPIOID ANALGESIC activity, ethylmorphine [ban] is the 3-ethyl ether of morphine, and is an OPIOID RECEPTOR AGONIST, with OPIOID ANALGESIC and ANTITUSSIVE activity. 

Capillary gas chromatography of morphine and codeine was described by Christophersen and Rasmussen in connection with their studies on flash heater derivatization of drugs for gas chromatographic analysis. Derivatization was found necessary for relative polar compounds such as morphine and codeine because of the often undesirable adsorption observed with glass capillary columns. Trimethylsilylation was performed with N,0-bis-(trimethylsilyl)acetamide and ethylmorphine was used as an internal standard for the quantitative determinations on a 20 m by 0.35 mm I.D. glass capillary, wall coated with SE-30. Calibration graphs for concentrations of 1-10 yg/ml in ethylacetate were constructed. The data obtained from the reproducibility test showed that at 5.0 pg/ml the relative standard deviation was 1.5 % for codeine and 4.3 % for morphine. 

Glass capillary gas chromatography was used by Christophersen and Rasmussen also for heroin. Whereas morphine, codeine, mono-acetyl morphine and ethylmorphine were derivatized with N,0-bis(trimethylsilylJacetamide with flash heater derivatization, heroin was not derivatized, but it was well separated from the other compounds mentioned, as well as caffeine and strychnine, which were found in the heroin samples analyzed. 

Thermochemical studies have been made by Leroy [394-5], The absorption spectrum of codeine in the visible [396-7] and in the ultraviolet [398-9] has been determined. The ultra-violet absorption curve, compared with those of morphine and thebaine is given in Mg. 1. That of ethylmorphine is closely similar [400]. 

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