Ephedrine ( lat. Ephedrinum - from the name of the main plant containing lat. Ephedra ) is a psychoactive poisonous alkaloid contained (along with pseudoephedrine and N-methylephedrine ) in various types of ephedra ( lat. Ephedra L. ), including ephedra of horsetail ( lat Ephedra equisetina ), growing in the mountainous regions of Central Asia and Western Siberia , and lat. Ephedra monosperma growing in Transbaikalia [1] [2] .
Ephedrine | |
---|---|
Are common | |
Systematic name | 2-methylamino-1-phenylpropanol-1 |
Traditional names | Ephedrine |
Chem. formula | C 10 H 15 N O |
Physical properties | |
condition | solid crystalline |
Molar mass | 165.24 g / mol |
Thermal properties | |
T. melt. | OK. 40 ° C |
T. Kip. | with ° C decomposition |
T. | 225 ° C |
Chemical properties | |
Solubility in the air | let's dissolve |
Water solubility | 2.8 g / 100 ml |
Chloroform solubility | let's dissolve |
Solubility in ethanol | 100 g / 100 ml |
Classification | |
Reg. CAS number | 299-42-3 |
Pubchem | |
Reg. EINECS number | |
SMILES | |
Inchi | |
CHEBI | |
Chemspider | |
Security | |
LD 50 | mice - 100 mg / kg |
Toxicity | highly toxic |
Content
History
Ephedrine in its natural form, known as Ma Huang ( Chinese trad. 麻黃 , Ex . , Pinyin : má huáng ), has been used in traditional Chinese medicine since the time of the Han Empire (206 BC - 220 g. AD.) as an anti-asthma drug and psychostimulant [3] . Ma Huang has been used as a treatment for asthma and bronchitis for centuries [4] .
For the first time, ephedrine was isolated from a two-spill cage in 1885 by Japanese chemist and pharmacologist Nagai Nagayoshi , but only in 1929 he synthesized it [5] . In addition to ephedrine, l- N-methylephedrine , d- pseudoephedrine , dN-methylpseudoephedrine and d-norseudoephedrine were also found in the plant [6] . The first synthesis of ephedrine was described by Shpet and Koller in 1925 [7] . The industrial production of ephedrine in China began in the 1920s , when Merck & Co. began selling a medicine known as ephetonin ( English ephetonin ).
Getting
Ephedrine can be obtained by extraction from natural raw materials, followed by purification from impurities.
The insignificant content of natural alkaloid ephedrine in various types of ephedra prompted chemists to develop synthetic methods for producing ephedrine. The first complete synthesis of ephedrine and its isomers was carried out by Shpet and Koller (1925) [7] .
Almost simultaneously, Manske, Johnson and Skit was presented a method of synthesis, which consists in the catalytic reduction of phenylmethyldiketone in the presence of methylamine , which gives ephedrine, free from pseudo-compounds [6] .
In another similar method, acyloin C₆H₅CHOHCOCH is obtained in optically active form by adding benzaldehyde to the fermenting sugar solution. Further condensation of this acyloin with methylamine and catalytic reduction gives optically active l-ephedrine [6] .
Later, a number of variants of the synthesis of ephedrine were proposed, but the following were found to be practical: benzene serves as the starting material, which is condensed with monochloropropionic acid chloride in the presence of aluminum chloride . The resulting chloroethyl phenyl ketone is condensed with methylamine , and a secondary amine is obtained, which, when reduced, forms ephedrine.
Ephedrine has two asymmetric carbon atoms , so there are four optically active isomers of ephedrine and two racemates . Of all the four isomers, ephedrine ( cis- isomer) and pseudoephedrine | ( trans- isomer), which are spatial isomers, are the most widely used.
The cis isomer is a levorotating alkaloid, the trans isomer is a dextrorotatory. The release of ephedrine from a synthetic product (racemate) is based on the different solubilities of their oxalates in alcohol. Ephedrine oxalate crystallizes from alcohol as a precipitate, and pseudoephedrine oxalate dissolves in alcohol.
Determining authenticity and quantity
The authenticity of ephedrine hydrochloride is determined [8] :
- reaction with a solution of silver nitrate in the presence of nitric acid; a white cheesy precipitate of AgCl silver chloride precipitates;
- by reaction with potassium ferricyanide in an alkaline medium - by the smell of benzaldehyde , resulting from the decomposition of ephedrine;
- by reaction with a solution of copper sulfate in the presence of alkali, a blue color is formed. When adding ether and shaking the vessel with the reaction mass, the pooled ether layer turns violet-red; the aqueous layer retains the blue color.
The quantitative content of ephedrine in the preparation can be determined by various methods, for example, by the method of acid-base titration in non-aqueous media in the presence of oxide mercuric acetate. It can be determined photo-colorimetrically by the colored complex with copper sulfate. You can use the method of neutralization and argentometry [8] .
Physical Properties
White needles or white crystalline powder of bitter taste.
Biological action
Ephedrine in the body of animals is a provocateur for the release of adrenaline and noradrenaline, mostly outside the CNS , as well as an inhibitor of MAO .
Medical application
Ephedrine as a means of systemic action and nasal vasoconstrictor is an outdated drug, in many countries recognized as ineffective and unsafe, as it can potentially cause drug dependence, as well as provoke diseases of the cardiovascular system.
Today it is used as a more long-acting substitute for adrenaline , with anemization and as part of anesthetic drugs of local action.
By its pharmacological action, it is a sympathomimetic that stimulates alpha and beta adrenoreceptors . Acting on varicose thickenings of efferent adrenergic fibers, promotes the release of norepinephrine into the synaptic cleft. In addition, it has a weak stimulating effect directly on adrenoreceptors. Causes vasoconstrictor , bronchodilatory and psychostimulating action. Increases total peripheral vascular resistance (OPSS) and systemic arterial pressure , increases the minute volume of blood circulation , heart rate and heart rate, improves AV conductivity ; improves skeletal muscle tone, blood glucose concentration. It inhibits intestinal peristalsis , dilates the pupil (without affecting the accommodation and intraocular pressure). Stimulates the central nervous system , the psychostimulant effect is close to amphetamine . Inhibits the activity of MAO and catecholamino-O-methyltransferase. It has a stimulating effect on the alpha adrenoreceptors of the blood vessels in the skin, causing narrowing of the dilated vessels, thus reducing their increased permeability, leading to a decrease in edema with urticaria.
The onset of the therapeutic effect after ingestion is 15–60 minutes, the duration is 3-5 hours, with intramuscular administration of 25–50 mg, 10–20 minutes and 0.5–1 hours, respectively. With repeated administration at a short interval (10–30 min), the pressure of ephedrine decreases rapidly ( tachyphylaxis occurs, which is associated with a progressive decrease in the reserves of norepinephrine in varicose thickenings). On the basis of the drug, many other drugs with similar pharmacological effects have been created, for example, cephedrine.
Ephedrine with regular regular use causes a loss of body weight, which was used in the past (and sometimes now - illegally). Illegal is the content of 15% ephedrine or ephedra extract in the preparation of dietary supplements for weight loss.
Legal Status
Ephedrine was previously used as a medicine, but now in Russia the storage, use and sale of ephedrine preparations with concentrations greater than 10% are limited. Ephedrine is on the list of IV precursors whose turnover in the Russian Federation is limited and for which special control measures are being established [9] .
Although ephedrine and pseudoephedrine themselves have a limited effect on the central nervous system [10] , they serve as an important raw material for the illegal handicraft production of drugs containing methamphetamine and ephedron . For this reason, the turnover of ephedrine, pseudoephedrine and preparations containing them is limited in many countries. In Russia, ephedrine and pseudoephedrine are included in the list of precursors of narcotic drugs [11] . Hand-made preparations of ephedrine are included as a narcotic drug in the List I of the List of Narcotic Drugs, Psychotropic Substances and their Precursors which are subject to control in the Russian Federation (circulation is prohibited).
Contrary to the ban, ephedrine is illegally imported into the Russian Federation for the production of drugs from the People's Republic of China. In 1996, about 90 kg of ephedrine were detained, and (according to expert estimates) about a ton were imported into the country - including through Mongolia and Kazakhstan [12] . Although in the People's Republic of China ephedrine is used in traditional medicine, they are shot for drug trafficking.
In the UN Convention against Illicit Drug Trafficking, ephedrine is included in Table I - substances that are directly used in the manufacture of drugs.
In the US, ephedrine as a substance has never been banned. In 1996, the Food and Drug Administration (FDA) imposed limits on the daily dosages of ephedra products, but in 2000 they lifted them. In 2004, the FDA imposed a ban on ephedra alkaloids, other than those used in medicines for asthma, colds, allergies, and two years later a ban was imposed on dietary supplements containing ephedrine. Ephedrine remains legal in other forms, but sales are limited (no more than 9 grams per month) and sellers are required to require identification and store information about customers and the amount of ephedrine sold by them (Combat Methamphetamine Epidemic Act of 2005).
In Germany, the use of ephedrine until 2001 was not limited. Then restrictions were introduced, because most consumers were unknown. And since April 2006, all drugs containing ephedrine, began to release only by prescription [13] .
Since 2008, in South Africa, ephedrine has been allowed to use in medicines for the treatment of colds - but not more than 8 mg per 1 tablet. And the use of ephedrine in other drugs (for weight loss) is completely prohibited [14] .
Notes
- ↑ Kharkevich D.A. Ephedrine // Great Medical Encyclopedia : 30 t. / Ch. ed. B.V. Petrovsky . - 3 ed. - Moscow: Soviet Encyclopedia , 1986. - T. 28. Economy - Foot and mouth disease . - 544 s. - 150 000 copies
- ↑ Ibragimov A.N. Ephedrine // Chemical Encyclopedia : 5 t. / Ed. Knunyants I.L. - Moscow: Soviet Encyclopedia , 1998. - T. 5. Tryptophan - Yatrohimiya. - 783 s. - 10 000 copies - ISBN 5-85270-310-9 .
- ↑ Woodburne O. Levy. The Principles of Health Laws and the Medical Practice / Norman S. Miller. - Academic Press, 26 February 2010. - p. 307–308. - ISBN 978-0-12-496736-6 .
- ↑ Ford MD, Delaney KA, Ling LJ, Erickson T. Clinical Toxicology. - Philadelphia: WB Saunders, 2001. - ISBN 0-7216-5485-1 .
- ↑ Jan Dirk Blom. Ephedrine and Hallucinations // A Dictionary of Hallucinations. - Springer Science & Business Media, 2009. - p. 175. - 553 p. - ISBN 978-1-44-191223-7 .
- ↑ 1 2 3 Course of Organic Chemistry / ed. M.N. Kolosova. - Leningrad: State Scientific and Technical Publishing House of Chemical Literature, 1960. - p. 1057-1058.
- ↑ 1 2 RHF Manske, HL Holmes. Ephedrine synthesis // The Alkaloids: Chemistry and Physiology. - Elsevier, 2014. - p. 352. - 430 p. - ISBN 978-1-48-322193-9 .
- ↑ 1 2 Efidrin hydrochloride (Inaccessible link) . The appeal date is February 7, 2013. Archived May 6, 2014.
- Resolution of the Government of the Russian Federation of June 30, 1998 No. 681 “On Approval of the List of Narcotic Drugs, Psychotropic Substances and their Precursors to be Controlled in the Russian Federation” (as amended and supplemented)
- ↑ Phyllis A. Balch, Robert Rister. Prescription for Herbal Healing .
- On approval of the list of narcotic drugs, psychotropic substances and their precursors subject to control in the Russian Federation .
- ↑ Alexander Platkovsky. China flunked Russia with drugs (Rus.) // Izvestia. - Moscow, 1997. - March 4 ( No. 62 ). - ISSN 0233-4356 .
- ↑ Verordnung zur Neuordnung der Verschreibungspflicht von Arzneimitteln (AMVVNV). Archived May 17, 2014. V. v. 21. Dezember 2005 BGBl. I S. 3632; Geltung ab 1. Januar 2006.
- ↑ Archived copy . The appeal date is April 18, 2009. Archived June 28, 2009.
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