Кокаин

Описание

Cocaine is best known as an illegal drug that produces a euphoric “high” in individuals who use it. Cocaine is an alkaloid obtained from the leaves of the coca plant, Erythroxylum coca, which is native to northwestern South America and Central America.

Химические свойства

Cocaine (also known as methylbenzoylepgonine), C17H21NO4, is a colorless-to-white crystalline substance, usually reduced to powder. Cocaine is soluble in alcohol, chloroform, and ether, slightly soluble in water, giving a solution slightly alkaline to litmus.

Физические свойства

Appearance: pure white crystal, odorless. Solubility: insoluble in water (1:600); soluble in chloroform (1:0.7), ethyl ether (1:3), ethanol (1:7), and other organic solvents; soluble in acetone, benzene, ethyl acetate, two carbonyl sulfide, and petroleum ether; show monoclinic flaky crystal in ethanol. Melting point: 98° (it can be slowly evaporated over 90°), the specific rotation of ?16°.

История

In 1855, cocaine was first extracted from the leaves of herbal ingredients and named Erythroxylon by the German chemist Friedrich (G. Friedrich) (1828–1890). In 1859, the German chemist Niemann (Albert Niemann) (1834–1861) defined a higher purity of material, named cocaine. In 1880, cocaine was used as a local anesthetic by the “father of modern surgery,” William Stewart Halsted. In 1884, cocaine was firstly recommended to be used as a local anesthetic, sexual stimulant, and antidepressant by Sigmund Freud, a famous psychologist in Austria (1856– 1939). He called it “a magical substance”

Использование

Use of cocaine is known since early times.It occurs in the South American coca leaves.Chewing of leaves mixed with lime was acommon practice among natives, who traveledgreat distances without experiencingfatigue (Cordell 1978). Cocaine is obtainedby extraction of coca leaves. It is also preparedby methylation and benzoylation of thealkaloid, ecgonine. The dilute aqueous solutionsof its hydrochloride is used as a topicalanesthetic in ophthalmology. Cocaine and itsderivatives are controlled substances listedin the U.S. Code of Federal Regulations(Title 21, Parts 321.1 and 1308.12, 1987).

Определение

cocaine: A powerful drug present inthe leaver of the coca plant (Erythroxyloncoca). It stimulates the centralnervous system and has effects similarto the amphetamines. It was originallyused as a local anaesthetic. Theillegal drug is usually the soluble hydrochloride.This can be convertedinto the free-base form (known ascrack cocaine) by dissolving in waterand heating with sodium bicarbonate.Cocaine is a class A drug in theUK. It can be detected by Scott’stest.

Методы производства

Colombia is the world’s leading producer of cocaine, with about 75% of the world’s production.Coca is grown locally and is also imported from Peru and Bolivia.the processing of coca involves mashing the leaves with a base, kerosene, and sulfuric acid to produce a pastecontaining between 40% and 70% cocaine. It can then be exported where it is dried andpurified into cocaine hydrochloride. Estimates of global consumption of cocaine vary, but areasonable approximation is roughly 750 tons. Of this amount, approximately one-third isimported into the United States, which is the leading consumer of cocaine.

Показания

It is mainly used for local anesthesia in various operations. It is also suitable for nasal, pharyngeal, ear, urethra, vagina, and other operations (with 5–10% solution). 2% to 3% solution is used for eye surgery.

Общее описание

Cocaine as a euphoriant–stimulant, psychotomimetic, anddrug of abuse could as well be discussed with amphetamineand methamphetamine, with which it shares many biologicalproperties. At low doses, it produces feelings of well-being,decreased fatigue, and increased alertness. Cocaine tends toproduce compulsive drug-seeking behavior, and a full-blowntoxic psychosis may emerge. Many of these effects appear tobe related to the effects of increased availability of DA for interactionwith postsynaptic receptors (D₂ and D₃ receptors arepertinent). Cocaine is a potent DA reuptake blocker, acting bycompetitive inhibition of the DAT. A phenethylamine moiety with added steric bulk may suffice for this action. An interactionbetween a hydrogen atom on the nitrogen of the protonatedform of cocaine and an oxygen of the benzoyl estergroup, or alternatively, an interaction between the unsharedelectron pair of the freebase nitrogen and the carbonyl of thebenzoyl ester group, could approximate this moiety.

Опасность

Poison; powerful central nervous system effects.

Механизм действия

Cocaine has been shown to block the reuptake of norepinephrine, serotonin, and dopamine; however, the reinforcing and stimulant nature of cocaine seems to be related primarily to blockade of dopamine reuptake, leading to the “ dopamine hypothesis” of cocaine's actions. [3H]Cocaine was used in an attempt to identify the “cocaine receptor,” and this was later shown to be similar to the dopamine transporter. Currently, it is thought that cocaine produces it reinforcing effects by interfering with dopamine reuptake by blocking the dopamine transporter. Although the human dopamine transporter has been cloned, it is unknown if the dopamine and cocaine binding domains are identical or how much they overlap.

Клиническое использование

Cocaine has a very interesting history. The coca plant was used by South American Indians for religious and mystical purposes and as a stimulant both to increase endurance and to alleviate hunger. It was introduced into Europe during the 1800s, and at the end of the 19th century, cocaine use was popular and socially acceptable. Various cocaine-containing preparations were available, and it also was used to “fortify” wines (e.g., Vin Coca). For a period of approximately 20 years, until just after the turn of the century, it was a constituent of the soft drink Coca-Cola. Additionally, cocaine was used for therapeutic reasons but was later supplanted by amphetamine.

Профиль безопасности

A human poison by ingestion and possibly other routes. Poison experimentally by ingestion, intraperitoneal, intravenous, subcutaneous, and parented routes. Human central nervous system effects by ingestion and possibly other routes: general anesthesia, hallucinations or distorted perceptions, and convulsions. An eye irritant. A widely abused, controlled substance. Abuse leads to habituation or addiction. In medcine, it is used as a local narcotic anesthetic applied topically to mucous membranes. The free base is solublein fats and thus is used for ointments and oily solutions. For water-soluble applications, the sulfate or hydrochloride is used. See also ESTERS. When heated to E decomposition it emits highly toxic fumes.

Метаболизм

Cocaine is active via nearly every possible route of administration; however, insufflation of “snow” or “coke” represents one of the most popular routes. Administered in this manner, peak effects and plasma levels are achieved within 30 minutes. Smoking the freebase form of cocaine (“crack”) results in an even more rapid effect. The freebase form rather than the hydrochloride salt is used for smoking, because the temperatures required for vaporization of the salt result in considerable decomposition. Intravenously administered cocaine can achieve peak blood levels within a few minutes. Cocaine is metabolized to benzoylecgonine, the methyl ester of ecgonine, and to a lesser extent, to ecgonine, norcocaine, and hydroxylated derivatives.

Методы очистки

(
)-Cocaine crystallises from EtOH and sublimes below 90o in a vacuum in an amorphous form. The hydrochloride crystallises from MeOH/Et2O with m 195o and [] D20 -72o (c 2 in H2O, pH 4.5), -78.5o (50% aqueous EtOH). [Sam & Reynolds J Chem Soc 97 1335 1910, Tufariello et al. J Am Chem Soc 101 2435 1979.] -Cocaine is the (+) enantiomer. [Beilstein 22 I 547, 22 II 150.]

использованная литература

Palit, Khare, Phytochem., 8, 1559 (1969)