Morphine basicity

Although their presentiy accepted stmctures were unknown, they were characterized with the tools available at the time. Because morphine (2, R = H), C22H22NO 3, was shown to have properties similar to the basic soluble salts obtained from the ashes of plants (alkah) it was categorized as a vegetable alkaU or alkaloid, and it is generally accepted that it was for this case the word was coined. 

Because of their basic properties, aikaioids were among the first naturai substances that eariy chemists extracted and purified. Morphine was isoiated from poppies in 1805 and was the first aikaioid to be characterized. When treated with aqueous strong acid, aikaioids accept protons to produce water-soiubie cations. The protonated aikaioids dissoive, ieaving the rest of the piant materiais behind. Adding strong base to the aqueous extract reverses the proton-transfer reaction, converts the aikaioid back to its neutrai base form, and causes pure aikaioid to precipitate from the soiution ... 

Colorimetric procedures used In steroid assays are often subject to drug Interference. In the determination of 17-Ketosterolds by the Zimmerman reaction, drugs with the 17-Keto basic structure such as ascorbic acid, morphine and reserplne will cause Increased values. In the determination of 17,21 -dlhydroxysterolds by the Porter-Sllber reaction the dlhydroxy-acetone chain Is the reactive unit. Drugs like meprobamate, chloral hydrate, chloropromazlne and potassium Iodide will Interfere with this reaction and cause elevated values. In the colorimetric determination of vanlllylmandellc acid (VMA) by a dlazo reaction, drugs like methocarbamol and methyl dopa cause... 

An indication that the SAR of the narcotic antagonists was more complex than had been anticipated came from the observation of the tremendous increase in milligram potency obtained by fusing an additional bicyclic ring onto the basic morphine structure. The... 

Many pharmacologically active organic chemicals fonnd in natnre are alkaloids. In general, these componnds contain one or more nitrogen atoms, which in turn impart some basicity to the molecnle. Well-known alkaloid examples are caffeine, cocaine, codeine, ephedrine, morphine, nicotine, qninine, and scopolamine. Heroin is derived from morphine by a chemical modification that increases lipophilicity, making the heroin molecnle inherently more pharmacologically potent than morphine. The exhibition of its basic properties by an alkaloid (Aik) involves (by definition) the acceptance of a proton H+ according to ... 

In the same period, vendors of proprietary medicines took advantage of our love of the natural to peddle a variety of plant-derived products. These were advertised as safer and more pleasant than those typically employed by physicians. For example, Mrs. Winslow s Soothing Syrup and Kopp s Baby Friend had morphine sulfate as their basic ingredient. Hostetter s Bitters was a 78 proof (39% ethanol) cocktail. This theme is being replayed currently as alternative medicine. This time around, controlled clinical trials are being carried out, slowly, to establish what works and... 

Fig. 4.3 CSF concentration/free (unbound) plasma concentration ratios for neutral and basic drugs 1, ritropirronium 2, atenolol 3, sulpiride 4, morphine 5, cimetidine 6, meto-prolol 7, atropine 8, tacrine 9, digoxin 10, propranolol 11, carbamazepine 12, ondansetron 13, diazepam 14, imipramine 15, digitonin 16, chlorpromazine and acidic drugs, a, salicylic acid b, ketoprofen c, oxyphenbutazone and d, indomethacin compared to log D.

Opium contains over 40 different alkaloids, all of which will be exuacted from opium by the procedure just described. It then remains to separate morphine from this mixture. Of the main opium alkaloids, only morphine displays some acidic properties as well as basic properties. Although a tertiary amine, morphine also contains a... 

Soaking plants parts in alcohol (ethanol) creates a tincture. In this process, pharmacologically active constituents of the plant are extracted by the alcohol. Tinctures do not contain the complete spectrum of substances that exist in the plant or crude drug, only those that are soluble in alcohol. In the case of opium tincture, these ingredients are alkaloids (i.e., basic substances of plant origin) including morphine, codeine, narcotine = noscapine, papaverine, narceine, and others. 

The determination of 17-ketosteroids is most often determined in the clinical laboratory by the Zimmerman reaction, in which the ether-extracted material is allowed to react with m-nitroaniline to yield a colored product. Thus, any compound with the 17-keto basic structure such as reserpine, morphine, ascorbic acid, or their metabolites will interfere. The Porter-Silber reaction used in the determination of 17,21-dihydroxysteroids is also not specific, and the reaction requires a di-hydroxyacetone side chain. Paraldehyde, chloral hydrate, meprobromate, and potassium iodide have been found to interfere, and patients should be maintained free of these drugs for 24-48 hours before the urine collection (Bll). 

Since milk is more acidic (pH 6.5) than plasma, basic compounds (e.g., alkaloids, such as morphine and codeine) may be somewhat more concentrated in this fluid. In contrast, the levels of weak organic acids will probably be lower than those in plasma. In general, a high maternal plasma protein binding of drug will be associ-... 

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