130-95-0 Usage
Pharmacology and mechanism of action
Quinine is the principal alkaloid of cinchona bark. The cinchona bark was first used against fever in Peru, probably around 1630, but the compound may have been used much earlier by the native Indians. Soon thereafter it was introduced into Europe[1]. Quinine is a stereoisomer of quinidine, which has similar antimalarial properties. It is a potent schizontocidal agent against all human plasmodial species. It is also gametocytocidal against P. vivax, P. ovale, and P. malariae but not against P. falciparum [1].
The mechanism of action is probably, as for chloroquine, an inhibition of haem polymerase (cf. Chloroquine) [2].
Indications
Different sources of media describe the Indications of 130-95-0 differently. You can refer to the following data:
1. Quinine is the drug of choice in the treatment of severe and complicated chloroquine-resistant P. falciparum malaria. It is also useful for the treatment of non-severe chloroquineresistant cases.
2. Quinine is one of several alkaloids derived from the
bark of the cinchona tree. The mechanism by which it
exerts its antimalarial activity is not known. It does not
bind to DNA at antimalarial dosages. It may poison the
parasite’s feeding mechanism, and it has been termed a
general protoplasmic poison, since many organisms are
affected by it.
Quinine is rapidly absorbed following oral ingestion,
with peak blood levels achieved in 1 to 4 hours.
About 70 to 93% of the drug is bound to plasma proteins,
depending on the severity of the infection.
Quinine is extensively metabolized, with only about
20% of the parent compound eliminated in the urine.
The primary present-day indication for quinine and
its isomer, quinidine, is in the intravenous treatment of
severe manifestations and complications of chloroquine-
resistant malaria caused by P. falciparum.
Aside from its use as an antimalarial compound,
quinine is used for the prevention and treatment of nocturnal
leg muscle cramps, especially those resulting
from arthritis, diabetes, thrombophlebitis, arteriosclerosis,
and varicose veins.
Side effects
Different sources of media describe the Side effects of 130-95-0 differently. You can refer to the following data:
1. The side effects of quinine commonly seen at therapeutic concentrations are known as cinchonism. In its mild form they include ringing in the ears (tinnitus), slight impairment of hearing, headache and nausea. The impairment of hearing is concentration-dependent and reversible [3]. More severe manifestations are vertigo, vomiting, abdominal pain, diarrhoea, marked auditory loss and different visual symptoms like diplopia and changed colour perception but also loss of vision. The visual disturbances are probably caused by ischemia in the retina and the optic nerve, and this can cause optic atrophy. In acute intoxication, CNS symptoms such as excitement, confusion, delirium, and hyperpnoea may occur, and permanent visual and hearing deficits are not uncommon. Quinine may aggravate hypoglycaemia due to malaria. Less frequent but more serious side effects of quinine include skin manifestations, asthma, thrombocytopenia, haemolysis, hepatic injury and psychosis [4, 5]. Patients with severe malaria attain and tolerate higher concentrations due to the concomitant reduction in free fraction.
2. 1, cinchona reaction: this can occur when the daily quinine dosage exceeds more than 1g or a little longer, manifested as nausea, vomiting, tinnitus, headache, vision hearing loss, generally being able to be restored after drug withdrawal
2, specific reaction: it can be observed of acute hemolysis, dermatitis, itching, angioneurotic edema and bronchial asthma. A small number of patients with falciparum malaria, after administrating quinine, can get chills, fever, vomiting, hemoglobinuria, urinary retention and other acute hemolytic disease, called black urine heat which can be fatal in severe cases.
3, intravenous injection, can inhibit the heart and further cause decreased blood pressure and life-threatening shock, thus it is strictly prohibited to adopt intravenous injection. Intravenous infusion should be administrated with caution. Intramuscular injection is prone to cause tissue necrosis, and thus is generally not used except in cases that oral administration is not doable.
3. Up to 25% of patients experience cardiac dysrhythmia, hypoglycemia,
cinchonism (tinnitus, vomiting, diarrhea, headache).
Severe effects, including hypotension and hypoglycemia, are
of particular importance in children, pregnant women and the
severely ill. Rarely, it can induce hemolytic anemia (‘blackwater
fever’). Quinine inhibits tryptophan uptake into cells.
4. Cinchonism describes the toxic state induced by excessive
plasma levels of free quinine. Symptoms include
sweating, ringing in the ears, impaired hearing, blurred
vision, nausea, vomiting, and diarrhea. Quinine is a potent
stimulus to insulin secretion and irritates the gastrointestinal
mucosa. Also, a variety of relatively rare
hematological changes occur, including leukopenia and
agranulocytosis. Quinine is potentially neurotoxic in
high dosages, and severe hypotension may follow its
rapid intravenous administration.
Contraindications and precautions
Quinine should be avoided in patients who are hypersensitive to the drug and should not be given to patients with optic neuritis and those with myasthenia gravis since it can aggravate these conditions. Digoxin clearance is decreased by quinine and the two drugs should not be combined unless plasma concentration monitoring of digoxin is feasible. Quinine causes ECG changes after large doses, and patients with cardiac diseases must be treated with caution. There is a possible risk for increased cardiovascular toxicity when quinine is given to patients taking mefloquine prophylaxis or to those who have received mefloquine treatment within the last two weeks, and continuous cardiovascular monitoring is recommended[5].Diabetic patients may need special monitoring. Dosage adjustments may be needed in patients with liver diseases [6] and older subjects [7].
Interactions
Quinine shares most of the actions of quinidine, and most of the drug interactions seen with quinidine may be encountered with quinine as well. Quinine increases digoxin plasma levels, probably by reducing its non-renal clearance. Cimetidine has been reported to reduce the clearance of quinine and prolong its elimination half-life [4].
Preparations
Numerous preparations (tablets, solution for injection) containing various quinine salts are available.
? Quinine hydrochloride (dihydrate). 123 mg equals 100 mg base.
? Quinine dihydrochloride. 123 mg equals 100 mg base.
? Quinine bisulphate (heptahydrate). 169 mg equals 100 mg base.
? Quinine sulphate (dihydrate). 121 mg equals 100 mg base.
description
Quinine, an alkaloid derived from the bark of the cinchona tree, is a blood schizontocidal agent that is more toxic than chloroquine.Quinine is used to treat malaria caused by Plasmodium falciparum. Plasmodium falciparum is a parasite that gets into the red blood cells in the body and causes malaria. Quinine works by killing the parasite or preventing it from growing. This medicine may be used alone or given together with one or more medicines for malaria.
Quinine should not be used to treat or prevent night time leg cramps. This medicine may cause very serious unwanted effects and should only be used for patients with malaria.It is administered parenterally to patients with severe or complicated malaria who cannot take drugs by mouth because of coma, convulsions or vomiting.
It is administered orally to less seriously ill patients with infections likely to be resistant to chloroquine or mefloquine, sometimes in combination with pyrimethamine/sulfadoxine or a tetracycline.
Quinine is an extremely basic compound and is, therefore, always presented as a salt. Various preparations exist, including the hydrochloride, dihydrochloride, sulphate, bisulphate, and gluconate salts; of these the dihydrochloride is the most widely used. Quinine has rapid schizonticidal action against intra-erythrocytic malaria parasites. It is also gametocytocidal for Plasmodium vivax and Plasmodium malariae, but not for Plasmodium falciparum. Quinine also has analgesic, but not antipyretic properties. The anti-malarial mechanism of action of quinine is unknown.
Uses
Different sources of media describe the Uses of 130-95-0 differently. You can refer to the following data:
1. Quinine is one of the oldest antimalarial drugs. At as early as the 15th century, the quinine-containing cinchona bark has been used extensively in the treatment of malaria with its antimalarial effect being similar to that of chloroquine that is through interfering with DNA synthesis effect. It is capable of inhibiting the erythrocytic stage of a variety of Plasmodium, being able to control the malaria symptoms. It also has certain killing effect on the gametes of vivax malaria and quartan malaria. However, it has no effect on the exoerythrocytic stage. Its major advantage is not easy to produce drug resistance, possibly due to that quinine binds the plasmodium DNA in a different way from chloroquine, so having no cross-resistance and can be used for the treatment of the infection of anti-chloroquine strains (especially Plasmodium falciparum). In addition, quinine can also exciting the uterus, inhibit the myocardium and have antipyretic analgesic effect. In addition to medicinal application, in analytical chemistry it can be used as the detection agent of bismuth, platinum and other metal ions and also be used for the separation agent of racemic organic acid.
2. Quinines use as an antimalarial agent spans several hundred years, but it has been replaced in recent years by other substances such as chloroquine. Because some Plasmodium strains have developed resistance to several malaria medications, quinine use is being revived. About 60% of quinine production is used for medicinal purposes, and the drug is available by prescription. In addition to its use as an antimalarial agent, quinine medications are used to treat leg cramps, muscle cramps associated with kidney failure, hemorrhoids, heart palpitations, and as an analgesic. At higher concentrations it is toxic and causes a condition known as cinchonism. Conditions associated with cinchonism include dizziness, hearing loss, visual impairment, nausea, and vomiting.Nonmedicinal use of quinine, accounting for about 40% of its use, is primarily as a fl avoringagent in condiments and liqueurs. The most common food use of quinine is tonic water. Tonicwater originated in India where English colonists drank carbonated water mixed with quinineto prevent malaria. The bitter taste of quinine was often masked by mixing it with alcoholicbeverages; one result of this practice was the drink gin and tonic. Current Food and DrugAdministration regulations in the United States limit the amount of quinine in tonic water to83 parts per million (83 mg per liter). This level is signifi cantly less than that required for therapeuticpurposes, so the use of commercial tonic waters to combat malaria is not practical.
3. Primary alkaloid of various species of Cinchona (Rubiaceae). Optical isomer of Quinidine. Antimalarial; muscle relaxant (skeletal)
4. Because of its relatively constant and well-known fluorescence quantum yield, quinine is also used in photochemistry as a common fluorescence standard. It has been used for imaging of oxygen evolution and oxide formation. Chloride and bromide have been sh
5. antimalarial, skeletal muscle relaxant
6. Quinine is a flavorant naturally obtained from the cinchona tree. it is
used as a bitter flavoring in beverages such as quinine water, tonic
water, and bitter lemon. quinine sulfate and quinine hydrochloride
are cleared for use as a flavor in carbonated beverages at levels less
than 83 ppm.
7. Quinine occurs in the dried stems or rootbarks of cinchona (Cinchona ledgerianaMoens). It is used in the treatment of malaria.It is also used as an analgesic and antipyreticagent.
pharmacokinetics
It can be subject to rapid and complete oral absorption with its plasma concentration being able to reach peak within 1 to 3 hours. It also has a plasma protein binding rate of about 70%. The concentration in the cerebrospinal fluid is about 2% to 5% of that in the plasma. It has a half-life of 7 to 8 hours. It can quickly penetrate through the placenta while the absorption through subcutaneous and intramuscular injection is slow. It is mainly subject to liver metabolism with about 5% of the dosage amount being excreted from the urine in the original form.
Clinically, quinine is mainly applied to the chloroquine-resistant patients infected with Plasmodium. Also used for the treatment of vivax malaria and falciparum malaria. Those for medical usage are all quinine salts. Sulfate can be used for oral administration while its hydrochloride is for injection. Until the 1920s, it had been an excellent anti-malaria drug. However, if used improperly, it can also cause poisoning, headaches, tinnitus, diarrhea, rash, vision and hearing disorders. It only has inhibitory effect on protozoan parasites without killing effect. The patient can still get relapse after being cured. To this end, scientists are still seeking more effective antimalarial drugs. Drugs currently in application include atabrine, plasmochin, chloroquinoline and so on. From a Chinese plant, antipyretic dichroa, people can extract a feerifuqine with its antimalarial effect being 100 times higher than quinine. However, it can’t be directly administrated due to the large toxicity. People are studying the structure and pharmacological effects of feerifuqine in order to find out the higher-efficacy antimalarial drugs.
Drug interactions
Different sources of media describe the Drug interactions of 130-95-0 differently. You can refer to the following data:
1. 1. It is not suitable to be used in combination with aminoglycoside antibiotics, furosemide and etacrynic acid
2. It is often used in combination with primaquine or pyrimethamine in order to achieve curing and enhance the effectiveness of the control of resistant strains.
2. Potentially hazardous interactions with other drugs
Anti-arrhythmics: flecainide levels increased;
increased risk of ventricular arrhythmias with
amiodarone - avoid.
Antibacterials: increased risk of ventricular
arrhythmias with moxifloxacin - avoid;
concentration reduced by rifampicin.
Antidepressants: possible increased risk of
ventricular arrhythmias with citalopram and
escitalopram.
Antimalarials: increased risk of convulsions with
mefloquine; avoid concomitant use with artemether/
lumefantrine.
Antipsychotics: increased risk of ventricular
arrhythmias with droperidol, pimozide, risperidone
and possibly haloperidol - avoid.
Antivirals: concentration possibly increased by
atazanavir, darunavir, fosamprenavir, indinavir and
tipranavir; concentration increased by ritonavir;
increased risk of ventricular arrhythmias with
saquinavir - avoid.
Cardiac glycosides: levels of digoxin increased (halve
maintenance dose).
Ciclosporin: decreased ciclosporin levels reported.
Cimetidine: may increase plasma levels of quinine.
Precautions
1. Large doses can easily lead to the damage of the eighth cranial nerve and optic nerve. Patients of deafness, vestibular disorders and optic neuritis should be disabled. Patients suffering from acute phlebitis, nephritis, diabetes, cardiovascular disease, bradycardia, atrioventricular blocking should be disabled. Large doses have the effect of teratogenic and exciting the uterine smooth muscle. Menstrual women and pregnant women should be disabled for using it. It can reduce the skeletal muscle excitability so patients of myasthenia gravis should be disabled.
2 It has effects of inhibiting the heart with Intravenous infusion being easily lead to shock and not suitable for usage. Upon intravenous infusion, the patients should subject to close observation in changes of blood pressure; intramuscular injection can cause tissue necrosis, so it should be adopted of the deep gluteal muscle injection. It is forbidden to use in combination with quinidine and chloroquine so as not to cause cardiac arrest.
overdose
The most frequently encountered signs of Quinine overdosage are:
Tinnitus, decreased auditory acuity and vertigo. Permanent deafness has resulted from exposure to toxic doses.
Amblyopia, constricted visual fields, diplopia and night blindness. Recovery is slow but usually complete.
Quinidine-like effects resulting in hypotension, conduction disturbances, anginal symptoms and ventricular tachycardia.
Hypoglycaemia.
A local irritant effect on the gastrointestinal tract resulting in nausea, vomiting, abdominal pain and diarrhoea.
A single oral dose greater than 3 g is capable of causing serious and potentially fatal intoxication in adults, preceded by depression of the central nervous system and seizures. Much smaller doses can be lethal in children.
Dysrhythmias, hypotension and cardiac arrest can result from the cardiotoxic action and ocular toxicity can lead to blindness.
Emesis should be induced and gastric lavage undertaken as rapidly as possible. Activated charcoal should then be administered.
Supportive measures, to be employed as necessary, include ventilation, and symptomatic treatment of dysrhythmias, cardiac failure and convulsions. No specific measures of proven efficacy exist to reduce the toxicity or to promote the excretion of quinine.
References:
1. Black RH, Canfield CJ, Clyde DF, Peters W, Wernsdorfer WH (1986). Quinine. In: Chemotherapy of Malaria, 2nd edn, edited by L.Bruce-Chwatt (Geneva: World Health Organization).
2. Slater AFG, Cerami A (1992). Inhibition by chloroquine of a novel haem polymerase enzyme activity in malaria trophozoites. Nature, 355, 167–169.
3. Karlsson KK, Hellgren U, Alván G, Rombo L (1990). Audiometry as a possible indication of quinine plasma concentrations during treatment of malaria. Trans R Soc Trop Med Hyg, 84, 765–767.
4. Antimalarials. Martindale, The Extra Pharmacopoeia, 30th edn (1993), (London: Pharmaceutical Press), pp. 408.
5. Quinine. Therapeutic Drugs, edited by Sir Colin Dollery (1991), (London: Churchill Livingstone), pp. Q8–Q13.
6. Karbwang J, Thanavibul A, Molunto P, Na Bangchang K (1993). The pharmacokinetics of quinine in patients with hepatitis. Br J Clin Pharmacol, 35, 444–446.
7. Wanwimolruk S, Chalcroft S, Coville PF, Campbell AJ (1991). Pharmacokinetics of quinine in young and elderly subjects. Trans R Soc Trop Med Hyg, 85, 714–717.
Description
Quinine, was the first known antimalarial. It is a 4-quinolinemethanol derivative bearing a
substituted quinuclidine ring. The use of quinine in Europe began in the seventeenth century, after
the Incas of Peru informed the Spanish Jesuits about the antimalarial properties of the bark of an evergreen mountain tree they called quinquina (later called cinchona, after Dona Franciscoa
Henriquez de Ribera [1576–1639], Countess of Chinchon and wife of the Peruvian Viceroy).
Chemical Properties
Different sources of media describe the Chemical Properties of 130-95-0 differently. You can refer to the following data:
1. Quinine is odorless, but has an intense, bitter taste
2. white to light yellow crystal powde
Physical properties
Appearance: white granular or microcrystalline powder. No smell, slightly bitter.
Solubility: easily dissolved in ethanol, chloroform, and ethyl. Slightly soluble in
water and glycerol. Melting point: 173–175 °C. Specific optical rotation: ?172°
(ETOH, C = 1).
Occurrence
Reported present in Cinchona officinalis.
History
Quinine is a white crystalline alkaloid best known for treating malaria. Quinine is derived from the bark of several species of trees in the genus Cinchona in the Rubiaceae family. Cinchona trees grow on the eastern slopes of the Andes Mountains at elevations of several thousand feet. Because these symptoms were associated with malaria, Cinchona bark powder was recognized as a possible treatment in the 1600s by Jesuit missionaries. After decades of
work by numerous investigators, quinine was finally isolated in 1820 by Pierre-Joseph Pelletier
(1788–1842) and Joseph-Bienaimé Caventou (1795–1877). The name quinine originates
from the native word for the Cinchona tree quina quina, which became the Spanish word
quino for cinchona. The development of organic synthesis in the middle of the 19th century
and the limited supply of quinine stimulated attempts to synthesize it. William Henry
Perkins’s (1838–1907) attempt to synthesize quinine in 1856 led to his discovery of mauve,
which was a signifi cant discovery in the dye industry (see Indigo).
Preparation
By reaction from cinchona bark (Cinchona officinalis), where it is present at approximately 8%.
Definition
Different sources of media describe the Definition of 130-95-0 differently. You can refer to the following data:
1. A poisonous
ALKALOID found in the bark of the cinchona
tree of South America. It is used in treating
malaria.
2. quinine: A white solid,C20H24N2O2·3H2O, m.p. 57°C. It is apoisonous alkaloid occurring in thebark of the South American cinchonatree, although it is now usually producedsynthetically. It forms saltsand is toxic to the malarial parasite,and so quinine and its salts are used to treat malaria; in small doses itmay be prescribed for colds and influenza.In dilute solutions it has apleasant astringent taste and is addedto some types of tonic water.
3. ChEBI: A cinchona alkaloid that is cinchonidine in which the hydrogen at the 6-position of the quinoline ring is substituted by methoxy.
Antimicrobial activity
Quinine inhibits the erythrocytic stages of human malaria parasites
at <1 mg/L, but not the liver stages. It is active against
the gametocytes of P. vivax, P. ovale and P. malariae, but not
P. falciparum. The dextrarotatory stereoisomer, quinidine, is
more active than quinine, but epiquinine (cinchonine) and epiquinidine
(cinchonidine) have much lower antimalarial activities.
Acquired resistance
Resistance is now widespread in South East Asia, where
some strains are also resistant to chloroquine, sulfadoxine–
pyrimethamine and mefloquine. Cross-resistance with mefloquine
has been demonstrated in P. falciparum, but genetic
polymorphisms associated with chloroquine resistance are
not associated with quinine resistance.
General Description
Quinine, a cinchona alkaloid found in the bark of the cinchona tree, is known for its anti-malarial property.
Hazard
Skin irritant, ingestion of pure substance
adversely affects eyes.
Health Hazard
The toxicity of quinine is characterized bycinchonism, a term that includes tinnitus,vomiting, diarrhea, fever, and respiratorydepression. Other effects include stimulationof uterine muscle, analgesic effect,and dilation of the pupils. Severe poisoningmay produce neurosensory disorders, causingclouded vision, double vision, buzzing of theears, headache, excitability, and sometimescoma (Ferry and Vigneau 1983). Death fromquinine poisoning is unusual. Massive dosesmay be fatal, however.LD50 value, oral (guinea pigs): 1800 mg/kg.
Flammability and Explosibility
Nonflammable
Pharmaceutical Applications
A quinolinemethanol from the bark of the Cinchona tree; the
laevorotatory stereoisomer of quinidine. Formulated as the
sulfate, bisulfate or ethylcarbonate for oral use and as the dihydrochloride
for parenteral administration. The salts are highly
soluble in water.
Biochem/physiol Actions
Potassium channel blocker
Pharmacology
In terms of its type of action, quinine is an antimalarial drug similar to chloroquine,
although it is inferior in its activity.
Like chloroquine, quinine binds with plasmodium DNA, thus interfering in the synthesis of nucleic acids and preventing its replication and transcription. Quinine also suppresses a large portion of the enzymatic system and therefore it is characterized as a
general protoplasmid toxin. This fact agrees well with the action of quinine on membranes,
its local anesthetizing and its cardiodepressive effects.
Upon oral administration, quinine effectively acts in combination with pyrimethamine,
sulfadiazine, and/or tetracycline for treating uncomplicated incidents of chloroquineresistant forms of P. falciparum. Because of the many associated side effects, its use is
extremely limited. Currently, the only indication for use is for forms of malaria that are
resistant to other synthetic drugs. Synonyms of this drug are bronchopulmin, nicopriv,
quinnam, and others.
Pharmacokinetics
Oral absorption: 80–90%
Cmax 600 mg oral: 5 mg/L after 1–3 h
Plasma half-life: 8.7 h
Volume of distribution: 1.8 L/kg
Plasma protein binding: c. 70%
Quinine is well absorbed by the oral route. Intramuscular
administration gives more predictable data than intravenous
administration and may be more useful in children. Plasma
protein binding rises to 90% in uncomplicated malaria and
92% in cerebral malaria due to high levels of acute-phase proteins.
Similarly, the elimination half-life rises to 18.2 h in severe
malaria. There is extensive hepatic metabolism to hydroxylated
derivatives. Urinary clearance is <20% of total clearance.
Clinical Use
Falciparum malaria (alone or in combination with tetracycline,
doxycycline, clindamycin or pyrimethamine–sulfadoxine)
Babesiosis (in combination with clindamycin)
It is particularly used in cerebral malaria if chloroquine resistance
is suspected (Ch. 62). It is not recommended for treatment
of uncomplicated falciparum malaria.
Safety Profile
Human poison by unspecified route. Experimental poison by subcutaneous, intravenous, intramuscular, and intraperitoneal routes. Moderately toxic experimentally by ingestion. An experimental teratogen. Human systemic effects by ingestion: visual field changes, tinnitus, and nausea or vomiting. Human teratogenic effects by ingestion: developmental abnormahties of the central nervous system, body wall, and musculoskeletal, cardovascular, and hepatoblltary systems. Experimental reproductive effects. Mutation data reported. Can cause temporary loss of vision. Quinine dermatitis is an occupational hazard to barbers particularly, and generally to people who work with quinine tonics, medcaments, or cosmetics. An irritant to mucous membranes. Combustible when exposed to heat or flame. Decomposes on exposure to light. When heated to decomposition it emits toxic fumes of NOx. Used to treat malaria.
Synthesis
Quinine, (5-vinyl-2-quinuclidinyl)-(6-methoxy-4-quinolyl)methanol (37.1.1.47), is isolated from the bark of the cinchona tree. One of the methods of making the ethyl ester of quininic acid (37.1.1.27) that should be mentioned is the method described in the following scheme. Reacting p-anisidine and acetoacetic ester in the presence of sulfuric acid gives 6-methoxylepidine (37.1.1.22). The hydroxyl group of this compound is replaced with a chlorine atom by reacting it with a mixture of phosphorus oxychloride and phosphorus pentachloride, giving 2-chloro- 4-methyl-6-methoxyquinoline (37.1.1.23). Reducing this compound with hydrogen using a palladium catalyst removes the chlorine atom at C2 and gives 4-methyl- 6-methoxyquinoline (37.1.1.24). Condensing this with benzaldehyde gives 2-(6-methoxy quinolinyl-4)-styrene (37.1.1.25), the double bond in which is oxidized using potassium permanganate to make 6-methoxyquinolinic acid—cinchonine (37.1.1.26), which is then converted into an ester (37.1.1.27) in the usual manner.
Another convenient way for preparation of quininic acid ethyl ester (37.1.1.27) is by using p-N-methylacetanisidine and diethyloxalate, which are reacted to form the p-N-methylacetaniside of oxalacetic acid (37.1.1.28). Heterocyclization of the product under acidic conditions leads to the formation of N-methyl-2-keto-4-carbethoxy-6-methoxyquinoline (37.1.1.29), which is reacted with a mixture of phosphorus oxychloride and phosphorus pentachloride to make 2-chloro-4-carboethoxy-6-methoxyquiniline (37.1.1.30). Reducing this with hydrogen using a palladium catalyst gives ethyl ester of 6-methoxyquinolinic acid (37.1.1.27).
Metabolism
Quinine is metabolized in the liver to the 2′-hydroxy derivative, followed by additional hydroxylation
on the quinuclidine ring, with the 2,2′-dihydroxy derivative as the major metabolite. This metabolite
has low activity and is rapidly excreted. The metabolizing enzyme of quinine is CYP3A4. With the
increased use of quinine and its use in combination with other drugs, the potential for drug
interactions based on the many known substrates for CYP3A4 is of concern.
Purification Methods
Crystallise the quinine from absolute EtOH. It has been used as a chiral catalyst (see previous entry). [Beilstein 23 H 511, 23 I 166, 23 II 416, 23 III/IV 3265, 23/13 V 395.]
References
Pelletier, Dumas., Ann. Chim. Phys., 15,291,1337 (1820)
Hesse., Annalen, 258, 133 (1890)
Fiihner., Arch. Pharm., 244, 602 (1906)
Seekles., Rev. Trav. Chim., 42, 72 (1923)
Kindler., Chem. Ztg., 56, 165 (1932)
Cohen.,J. Chem. Soc., 999 (1933)
Velter., Festschrift., 542 (Basle, 1936)
Woodward, Doering.,J. Amer. Chem. Soc., 67,860 (1945)
Pharmacology :
Acton, King., Biochem. J., 15,53 (1921)
Sterkin, Helfgat., Biochem. Zeit., 207, 8 (1929)
Wagenaar.,Pharm. Weekbl., 66, 177, 197,250,261 (1929)
Wagenaar., ibid, 71,316 (1934)
Monnet., J. Pharm. Chim., 18, 94 (1933)
Buttle, Henry, Trevan., Biochem. J., 28,426 (1934)
Seeler, Dusenbery, Malanga.,J. Pharm. Exp. Ther., 78, 159 (1943)
Marshall., ibid, 85, 299 (1945)
Check Digit Verification of cas no
The CAS Registry Mumber 130-95-0 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,3 and 0 respectively; the second part has 2 digits, 9 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 130-95:
(5*1)+(4*3)+(3*0)+(2*9)+(1*5)=40
40 % 10 = 0
So 130-95-0 is a valid CAS Registry Number.
InChI:InChI=1/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3/p+1/t13-,14-,19-,20+/m0/s1
