Atropine characteristics

The importance of tropinone as a possible starting-point for the production of the therapeutically valuable alkaloids atropine, hyoscyamine, cocaine, tropacocaine and the artificial tropeines (p. 73) led Robinson to consider the possibility of preparing this substance by a simple method. Starting with the idea that the formula for tropinone (XXX) may be regarded as made up of the formulae of the residues of succindialdehyde (XXVII), methylamine (XXV III) and acetone (XXIX), he found that a mixture of these substances in water, when allowed to stand for thirty minutes produced tropinone, which could be detected by means of its characteristic dipiperonylidene derivative (bright yellow needles, m.p. 214°). 

The five routes presented (A-E) can be detected in the mass spectra of all 3-hydroxytropane esters. However, their contribution to the general fragmentation may vary widely. Table XIII shows the relative intensities of the characteristic peaks, corresponding to the ions a-g given below for atropine 26 (Fig. 8). Route A strongly dominates the fragmentation of pyranotropane alkaloids, leading in the case of strobiline (112), for example, to the ion m/z 162 (ion e) (base peak) (Scheme 30). 

Fig. 8. The most characteristic ions in the mass spectral fragmentation of atropine (26).

Despite the gastrointestinal absorption characteristics discussed above, it is common for absorption from the alimentary tract to be facilitated by dilution of the toxicant. Borowitz et al. (1971) have suggested that the concentration effects they observed in atropine sulfate, aminopyrine, sodium salicylate, and sodium pentopar-bital were due to a combination of rapid stomach emptying and the large surface area for absorption of the drugs. 

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. 

Tertiary amines used for their antispasmodic properties are dicyclomine hydrochloride (Ben-tyl, others), oxyphencyclimine hydrochloride (daricon), flavoxate hydrochloride (Uripas), and oxyburynin chloride (Ditropan). The latter two are indicated specifically for urological disorders. These agents appear to exert some nonspecific direct relaxant effect on smooth muscle. In therapeutic doses they decrease spasm of the gastrointestinal tract, biliary tract, ureter, and uterus characteristic atropine-like effects on the salivary glands and the eye also are seen with oxybutynin. 

The enantioselective procedure of John et al. was also originally applied to monitor concentration-time profiles of atropine and hyoscyamine variants in a PK study in healthy swine (Table 5) [47], Mass spectrometric characteristics with respect to precursor and product ions of atropine and hyoscyamine are summarized in Table 9. Following single i.v. administration of 100 ug/kg, maximum plasma concentrations were found to be 48 ng/ml for atropine and 24 ng/ml for both enantiomers, the dis-tomer /Miyoscyamine and the eutomer. S -hyoscyamine, In contrast to data in human, no stereoselective preference for elimination was found in swine thus substantiating the assumption that hyoscyamine kinetics in man differ from that in swine. 

Inhaled ipratropium [i pra TROE pee um], a quaternary derivative of atropine (see Figure 22.5, p. 220), is useful in treating asthma and chronic obstructive pulmonary disease in patients unable to take adrenergic agonists. Ipratropium is also used in the management of chronic obstructive pulmonary disease (see p. 222). Important characteristics of the muscarinic antagonists are summarized in Figure 5.6. 

The first part of the research to be reported was the study of the metabolic faces of labeled cropic acid and atropine In mice and rats (91,92). Mice and rats given Incraperlconeal Injections of alpha-[ C]tropic acid at 1 mg/kg excreted In their urine only a single labeled compound that had essentially the same chromatographic characteristics as authentic tropic acid. The excretion of administered in this form was complete within about 2.5 h In the mice and within slightly more than 3 h In the rats. 

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