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With excessive dosage, tremors, convulsions and increased body temperature are observed. Overdoses cause tachyarrhythmias and a marked elevation of blood pressure, which can be life- threatening. Thus, receptors disappear from the cell surface or reappear on it, resulting more or less in an . However, studies suggest cocaine abusers do not show normal age- related loss of striataldopamine transporter (DAT) sites, suggesting cocaine has neuroprotective properties for dopamine neurons. Depression with suicidal ideation may develop in very heavy users. Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long term damage of dopamine neurons. All these effects contribute a rise in tolerance thus requiring a larger dosage to achieve the same effect. Physical withdrawal is not dangerous, and is in fact restorative. Physiological changes caused by cocaine withdrawal include vivid and unpleasant dreams, insomnia or hypersomnia, increased appetite and psychomotor retardation or agitation. A common but untrue belief is that the smoking of cocaine chemically breaks down tooth enamel and causes tooth decay. However, cocaine does often cause involuntary tooth grinding, known as bruxism, which can deteriorate tooth enamel and lead to gingivitis. Since saliva is an important mechanism in maintaining one's oral p. H level, chronic stimulant abusers who do not hydrate sufficiently may experience demineralization of their teeth due to the p. H of the tooth surface dropping too low (below 5. Due to the absorption of the cocaine from cocaine hydrochloride, the remaining hydrochloride forms a dilute hydrochloric acid. Cocaine dependency may result in physiological damage, lethargy, psychosis, depression, akathisia, and fatal overdose. Since then, Robert Robinson and Edward Leete have made significant contributions to the mechanism of the synthesis. The major contribution of L- ornithine and L- arginine as a precursor to the tropane ring was confirmed by Edward Leete. In animals, however, the urea cycle derives putrescine from ornithine. L- ornithine is converted to L- arginine. Hydrolysis of the imine derives N- carbamoylputrescine followed with hydrolysis of the urea to form putrescine. The separate pathways of converting ornithine to putrescine in plants and animals have converged. A SAM- dependent N- methylation of putrescine gives the N- methylputrescine product, which then undergoes oxidative deamination by the action of diamine oxidase to yield the aminoaldehyde. Schiff base formation confirms the biosynthesis of the N- methyl- . The second addition occurs through a Claisen condensation. This produces a racemic mixture of the 2- substituted pyrrolidine, with the retention of the thioester from the Claisen condensation. In formation of tropinone from racemic ethyl . The stereoselectivity of this reaction was further investigated through study of prochiral methylene hydrogen discrimination. The tropane ring system undergoes hydrolysis, SAM- dependent methylation, and reduction via NADPH for the formation of methylecgonine. The benzoyl moiety required for the formation of the cocaine diester is synthesized from phenylalanine via cinnamic acid. Hemscheidt proposes that Robinson's acetonedicarboxylate emerges as a potential intermediate for this reaction. Decarboxylation leads to tropane alkaloid formation. TRI produces tropine and TRII produces pseudotropine. Due to differing kinetic and p. H/activity characteristics of the enzymes and by the 2. TRI over TRII, the majority of the tropinone reduction is from TRI to form tropine. Cocaine appearing in powder form is a salt, typically cocaine hydrochloride (CAS 5. Street market cocaine is frequently adulterated or “cut” with various powdery fillers to increase its weight; the substances most commonly used in this process are baking soda; sugars, such as lactose, dextrose, inositol, and mannitol; and local anesthetics, such as lidocaine or benzocaine, which mimic or add to cocaine's numbing effect on mucous membranes. Its texture will also depend on the adulterants, origin and processing of the powdered cocaine, and the method of converting the base. It ranges from a crumbly texture, sometimes extremely oily, to a hard, almost crystalline nature. The hydrochloride (HCl) salt of cocaine is by far the most commonly encountered, although the sulfate (- SO4) and the nitrate (- NO3) are occasionally seen. Different salts dissolve to a greater or lesser extent in various solvents – the hydrochloride salt is polar in character and is quite soluble in water. It is practically insoluble in water whereas hydrochloride salt is water soluble. Some research suggests that smoking freebase cocaine can be even more cardiotoxic than other routes of administration. It is further refined through aqueous- solvent Liquid- liquid extraction. The smoke produced from cocaine base is usually described as having a very distinctive, pleasant taste. This effectively destroys some of the cocaine, and yields a sharp, acrid, and foul- tasting smoke. The free and legal commercialization of dried coca leaves under the form of filtration bags to be used as . Visitors to the city of Cuzco in Peru, and La Paz in Bolivia are greeted with the offering of coca leaf infusions (prepared in tea pots with whole coca leaves) purportedly to help the newly arrived traveler overcome the malaise of high altitude sickness. The effects of drinking coca tea are a mild stimulation and mood lift. It does not produce any significant numbing of the mouth nor does it give a rush like snorting cocaine. In order to prevent the demonization of this product, its promoters publicize the unproven concept that much of the effect of the ingestion of coca leaf infusion would come from the secondary alkaloids, as being not only quantitatively different from pure cocaine but also qualitatively different. In one controversial study, coca leaf infusion was used - in addition to counseling- to treat 2. Lima, Peru. Relapses fell from an average of four times per month before treatment with coca tea to one during the treatment. The duration of abstinence increased from an average of 3. These results suggest that the administration of coca leaf infusion plus counseling would be an effective method for preventing relapse during treatment for cocaine addiction. This is mostly done with the small amounts of cocaine remaining on a surface after insufflation. Another oral method is to wrap up some cocaine in rolling paper and swallow (parachute) it. This is sometimes called a . The juices are absorbed slowly by the mucous membrane of the inner cheek and by the gastrointestinal tract when swallowed. Alternatively, coca leaves can be infused in liquid and consumed like tea. Ingesting coca leaves generally is an inefficient means of administering cocaine. Advocates of the consumption of the coca leaf state that coca leaf consumption should not be criminalized as it is not actual cocaine, and consequently it is not properly the illicit drug. Because cocaine is hydrolyzed and rendered inactive in the acidic stomach, it is not readily absorbed when ingested alone. Evernote Sticky Notes - Download. With Evernote Sticky Notes you can pin important Evernote notes to your Desktop! Your notes stay always in sight so you won't forget them. Every note can have a custom color assigned to make it more distinguished from the other notes. 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