Atropine, degradation

The phannacokinetics of S- and / -enantiomers of hyoscyamine in humans have been examined by LC-ESI-MS/MS [13]. Plasma supplemented with atropine was incubated with human serum (not containing atropinesterase (AtrE)) and with rabbit serum possessing AtrE (EC 3.1.1.10), which stereospecificaUy hydrolyzes 5-hyoscyamine into tropine and tropic acid while leaving / -hyoscyamine unaffected. The estimation of the differences between the total hyoscyamine content in the aliquots incubated with human and rabbit sera allowed the determination of the remaining / -hyoscyamine and hydrolyzed S-hyoscyamine. Both enantiomers were detected in the MRM mode. The method proved to be reproducible, precise (RSD 2-9 %), accurate (93-101 %), and selective. The enantioselective assay was applied to the analysis of atropine degradation in rabbit semm in vitro as well as to human in vivo plasma samples from a pesticide-poisoned patient treated with atropine. The method was also applied for kinetic studies of atropine administered to swine, where no obvious stereoselective elimination was found [82]. 

Oxidation of ecgonine (2) by means of chromium trioxide was found to afford a keto acid (3). This was formulated as shown based on the fact that the compound undergoes ready themnal decarboxylation to tropinone (4)The latter had been obtained earlier from degradative studies in connection with the structural determination of atropine (5) and its structure established independently. Confirmation for the structure came from the finding that carbonation of the enolate of tropinone does in fact lead back to ecgonine. Reduction, esterification with methanol followed by benzoylation then affords cocaine. 

The degradation of atropine has been examined in Pseudomonas sp. strain AT3 and produces tropine as the initial metabolite. The degradation of this proceeds by oxidative... 

Pharmacologically, carbofuran inhibits cholinesterase, resulting in stimulation of the central, parasympathetic, and somatic motor systems. Sensitive biochemical tests have been developed to measure cholinesterase inhibition in avian and mammalian brain and plasma samples and are useful in the forensic assessment of carbamate exposure in human and wildlife pesticide incidents (Bal-lantyne and Marrs Hunt and Hooper 1993). Acute toxic clinical effects resulting from carbofuran exposure in animals and humans appear to be completely reversible and have been successfully treated with atropine sulfate. However, treatment should occur as soon as possible after exposure because acute carbofuran toxicosis can be fatal younger age groups of various species are more susceptible than adults (Finlayson et al. 1979). Carbofuran labels indicate that application is forbidden to streams, lakes, or ponds. In addition, manufacturers have stated that carbofuran is poisonous if swallowed, inhaled, or absorbed through the skin. Users are cautioned not to breathe carbofuran dust, fumes, or spray mist and treated areas should be avoided for at least 2 days (Anonymous 1971). Three points are emphasized at this juncture. First, some carbofuran degradation... 

Kirchoff, C., Bitar, Y., Ebel, S., and Holzgrabe, U. (2004). Analysis of atropine, its degradation products and related substances of natural origin by means of reversed phase high performance liquid chromatography./. Chromatogr. A 1046, 115-120. 

U. Lund and S. H. Hansen, Simultaneous determination of atropine and its acidic and basic degradation products by mixed-column HPLC, J. Chromatogr., 767 371 (1978). 

Enzymatic degradation of several TTA and QTA by atropinesterase from rabbit serum was investigated by John et al. [50], It was found that all TTA tested (atropine, 5-hyoscyamine, littorine, scopolamine, homatropine and cocaine) were hydrolysed (ester cleavage) by atropinesterase with different velocities... 

The modes of action of different alkaloids are diverse. For example, nicotine binds to and affects nicotinic acetylcholine receptors and shows toxicity. A recent molecular 3D model suggests that both acetylcholine and nicotine bind to the same pocket formed in a nicotinic acetylcholine receptor.15 Morphine binds to and activates opioid receptors, transmembrane-spanning G protein-coupled receptors, in the central nervous system of humans.16 Caffeine, which is structurally similar to adenine, inhibits cyclic AMP phosphodiesterase activity and inhibits the degradation of cAMP, thus exerting a toxic effect on insects 17 in human beings, binding of caffeine to the adenosine A2A receptor induces wakefulness.18 Atropine binds to muscarinic acetylcholine receptors, competing with acetylcholine, and blocks neurotransmission.1... 

Regarding the 16 compounds for which Incapacitating doses—usually calculated as the doses required to degrade the score In the Humber Facility Test to not more chan lOZ of the predose score—were given, three routes of administration were used Intramuscular Injection, Intravenous Injection, and Ingestion The most effective of the compounds Injected Intramuscularly was 3"qulnuclldlnyl benzllate, followed In order by EA 3443, EA 3580, 3-qulnuclidlnyl-L-(phenyl-cyclopentyl) >glycolace, L-2-alpha-troplnyl-L-(phenylcyclopencyl)-glycolate, L-l-alpha-croplnyl benzllate, scopolamine, 302,196, atropine, and Dlcran. 

Magnesium oxide is a basic compound and as such can react with acidic compounds in the solid state to form salts such as Mg(ibuprofen)2 or degrade alkaline-labile drugs. Adsorption of various drugs onto magnesium oxide has been reported, such as antihistamines, antibiotics (especially tetracyclines), salicylates, atropine sulfate, hyoscyamine hydrobromide, paracetamol, chloroquine, and anthranilic acid derivatives have been reported to adsorb onto the surface of magnesium... 

Most of the work performed so far on tropine alkaloids concerns the analysis of such alkaloids in pharmaceutical preparations (Table 4.5). Special methods have been investigated in order to lower the detection limit of such alkaloids 13 16 28,33,35,37,41,43,45 Revl-ews on the application of derivatization techniques in LC given by Frei and Santi1 and Frei3 , include some examples of tropine alkaloids. The analysis of atropine and its degradation products has also been investigated 3 3 3 . 

RETENTION DATA AND DETECTION LIMITS FOR ATROPINE AND ITS DEGRADATION PRODUCTS32... 

A.apoA.trop ac.atrop ac.B.B-isatropic ac Separation atropine Lichrosorb RP8,5um and degradation products (Table 4.3) 100x4.6 0.01M tetrabutylammonium in 0.05H aq. acetate buffer-ACN (4 1)(pH 5.5) 25... 

A,H,S,a-B,B-B,apoA, trop ac.atrop ac, B-isatropic ac Determination atropine and its degradation products (Table 4.1,Fig.4.2) Nucleosil 5CN and Nucleosil 5NH, in series c 50x4.6 He0H-0.025M NaOAc buffer (pH 5)(1 3) 32... 

Tropinic acid, CgHi 30i,N, is a degradation product of atropine, an alkaloid of the deadly nightshade, Atropa belladonna. It has a neutralization equivalent of 94 1. It does not react with benzenesulfonyl chloride, cold dilute KMnOj, or Br2/CCl. Exhaustive raethylation gives the following results ... 

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