Atropine, chemical structure

FIG. 18 Chemical structures of (a) acetylcholine chloride, (b) carbamylcholine chloride, (c) carba-myl-y8-methylcholine chloride, (d) acetyl-/i-methylcholine chloride, (e) tetramethylammonium chloride, (f) tetraethylamonium chloride, (g) succinylcholine chloride, (h) hexamethonium chloride, (i) scopolamine hydrobromide, 0 atropine sulfate, (k) homatropine hydrochloride, and (1) tubocurar-ine chloride. 

An alkaloid is a complex organic chemical substance found in plants, which characteristically combines nitrogen with other elements, has a bitter taste, and typically has some toxic, stimulant, analgesic effects. There are many different alkaloids, 30 of which are found in the opium plant. While morphine is the most important alkaloid in opium—for its natural narcotic qualities as well as providing the chemical structure for heroin—another alkaloid, codeine, is also sought after for its medicinal attributes. Other alkaloids include papaverine, narcotine, nicotine, atropine, cocaine, and mescaline. While the concentration of morphine in opium varies depending on where and how the plant is cultivated, it typically ranges from 3 percent to 20 percent. 

The octanol-water partition coefficient (Kow), characterizing distribution of a non-ionized compound between an octanol (o) and an immiscible aqueous (w) layer, may function as a measure of lipophilicity, that is often listed as its logarithmic value (log P). Therefore, log P may be used as a predictor of extractability in LLE. Table 1 presents log P values of TA calculated by the Molinspiration software [25] using SMILES notation for chemical structures. The SMILES concept is addressed in the next section [26], Conformity of calculated (calc.) and experimental (exp.) log P values is satisfying, as exemplarily shown for atropine (1.83 exp. [27] 1.77 calc.) and scopolamine (0.98 exp. [22] 1.05 calc.). 

The traditional method of drag development, at least in this century, has been to develop leads by first using, and then by isolating and identifying, the active chemical constituents from natural products, some of which may have been medicinally in use since antiquity. With the advent of modem organic chemistry some of these purified compounds were used directly (e.g., morphine, cocaine, atropine, quinine), and, once their chemical structures were ascertained, they became leads for hoped-for chemical modifications to achieve improved efficacy, less toxicity, or, at least, higher potency (e.g., dihydromorphinone, homatropine, acetylsalicylic acid). 

In the year 1939, Schaumann first identified and recognized the presence of a quatemaiy-carbon-atom in the morphine molecule, whieh eventually formed an altogether new basis and opened up a new horizon in the field of drug design ofnareotie analgesics. Intensive research further led to the evolution of pethidine (meperidine) which incidentally combines both the properties of morphine and atropine. It possesses a quaternary carbon-atom and quite astonishingly a mueh simpler chemical structure to that of morphine. 

Ptomaines. Name, derived from modern Greek ptoma=cadaver, for the so-called cadaveric poisons formed from putrefying proteins. The enzymatic decarboxylation products of the amino acids lysine and L-omithine ( cadaverine and putrescine), previously known as R, are, however, relatively non-toxic biogenic amines. Today the name P. is used for the toxic metabolic products of putrefactive bacteria that colonize rotting, protein-containing foodstuffs such as meat, fish, etc. These P. have widely differing chemical structures their activities are purported to be similar to those of the plant toxins such as strychnine, atropine, etc.. 

The chemical structure of alkaloids varies from relatively simple, e.g. atropine (racemic hyoscyamine). 

Although not usually classified as a glycolate, the structure of atropine (Fig. 57) can be visualized as such, taking certain liberties with the rules of chemical nomenclature. 

Fig. 3.13 The ACE50 method demonstrated for a mixture of ligands at 1 tM per component to the M2 receptor at 5 pM concentration. (A) NGD-3350 requires the greatest competitor concentration to be competed from the receptor, indicating that it is the highest affinity ligand. (B) Ratio plots indicate direct binding competition with atropine. (C) Select compound structures. Reprinted from [39] with permission from the American Chemical Society.

Once the structure of atropine (and other alkaloids) was known, exploratory chemical modifications become possible to ascertain the structural parameters within which anticholinergic properties existed and to exploit this knowledge to improve atropine. 

The limited quantities of teloidine so far available have precluded an investigation of its structure. However, from the marked similarity of its chemical reactions with those of tropine and oscine and from the association of meteloidine with atropine and 1-scopolamine in Datura meteloides, teloidine was considered to be one of the stereoisomers of the trihydroxytropane, XCI. This has been confirmed by synthesis. Teloidinone, the Cj-ketone of teloidine, has been synthesized (3) (mesotartaric aldehyde, methylamine, and acetonedicarboxylic acid) under physiological conditions. Teloidine and an isomer were formed in the reduction of this ketone. 

Aluminum hydroxide is constipating but is not related chemically to meperidine magnesium hydroxide is a strong laxative. The two antidiarrheal drugs that are structurally related to opioids are diphenoxylate and loperamide. Loperamide is available over-the-counter diphenoxylate is mixed with atropine alkaloids, and the product (Lomotil, others) requires a prescription. The answer is (C). 

The classic chemical prototype for the antimuscarinics is atropine, an alkaloid from/Afropa belladonna. Buried within its structure is the amino alcohol ester pharmacophore, where Ri is a hydroxymethyl group, R2 is a hydrogen, and the nitrogen is part of a bicyclic ring system called tropine (Fig. 44.17). 

Alkaloids were known in ancient times because they are easy to extract from plants and some of them have powerful and deadly effects. Any plant contains thousands of chemical compounds, but some plants, like the deadly nightshade, can be mashed up and extracted with aqueous acid to give a few compounds soluble in that medium, which precipitate on neutralization. These compounds were seen to be hke atkah and in 1819 Meissner, the apothecary from Halle, named them alkaloids. Lucrezia Borgia already knew all about this and put the deadly nightshade extract atropine in her eyes (to make her look beautiful atropine dilates the pupils) and in the drinks of her political adversaries to avoid any trouble in the future. Now, we would simply say that they are basic because they are amines. Below is a selection with the basic amino groups marked in black. Natural products are often named by a combination of the name of the organism from which they are isolated and a chemical part name. These compounds are all amines so all their names end in -ine. They appear very diverse in structure but all are made in nature from amino acids. 

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