- Product Name:
- Yohimban-16-carboxylic acid, 11,17-dimethoxy-18-(3,4,5-trimethoxybenzoyl)oxy-, methyl ester, (3.beta.,16.beta.,17.alpha.,18.beta.,20.alpha.)-
- RESERPINE extrapure
- Reserpine Standard for LC-MS
- Product Categories:
- chemical reagent
- pharmaceutical intermediate
- reference standards from Chinese medicinal herbs (TCM).
- standardized herbal extract
- Chiral Reagents
- Intermediates & Fine Chemicals
- Miscellaneous Natural Products
- Indole Alkaloids
- Asymmetric Synthesis
- Chiral Building Blocks
- Complex Molecules
- Mol File:
Reserpine Chemical Properties
- Melting point:
- ~265 °C (dec.)
- D23 -118° (CHCl3); D26 -164° (c = 0.96 in pyridine); D26 -168° (c = 0.624 in DMF)
- Boiling point:
- 655.12°C (rough estimate)
- 1.2336 (rough estimate)
- refractive index
- 177 ° (C=1, DMF)
- Flash point:
- storage temp.
- Inert atmosphere,Room Temperature
- Practically insoluble in water, very slightly soluble in ethanol (96 per cent).
- 6.6(at 25℃)
- optical activity
- [α]20/D 123±3°, c = 1% in chloroform
- Water Solubility
- Soluble in water.
- Stable, but darkens slowly in light. Combustible. Incompatible with strong acids, reducing agents, oxidizing agents.
- CAS DataBase Reference
- 3 (Vol. 24, Sup 7) 1987
- NIST Chemistry Reference
- EPA Substance Registry System
- Reserpine (50-55-5)
Reserpine Usage And Synthesis
Reserpine is an indole alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. It is an antipsychotic, and antihypertensive drug that used for the control of high blood pressure and for the relief of psychoticsymptoms[1-4]. However, its adverse effects have limited its clinical use. The antihypertensive actions of reserpine results from its ability to deplete catecholamines(among other monoamine neurotransmitters) from peripheral sympathetic nerve endings[2-4]. Moreover, reserpine also has a peripheral action in many parts of the body, resulting in a preponderance of the effects of the cholinergic part of the autonomous nervous system on the GI tract, smooth muscles, blood vessels, etc.
Reserpine is a drug used for the treatment of hypertension[4, 5,7, 8] and schizophrenia[although rarely used nowadays][4, 6]. It can also be used as an anticholinergic drug to combat excessive cholinergic activity in many parts of the body as well as parkinsonism. Reserpine can be used as sedative for horses in veterinary field. It is used as a long-acting tranquilizer to subdue excitable or difficult horses and has been used illicitly for the sedation of show horses, for-sale horses, and in other circumstances where a "quieter" horse might be desired. In addition, it can be used frequently as a highly useful analytic reference standard in the field of mass spectrometry owing to its availability, ease of ionization under electrospray conditions and stability in solution.
Mode of action
Reserpine is an adrenergic blocking agent used to treat mild to moderate hypertension through disrupting the normal process norepinephrine vesicular storage. The antihypertensive actions of Reserpine are a result of its ability of depleting catecholamines from peripheral sympathetic nerve endings[12-14]. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral resistance. Reserpine takes effect through inhibition of the ATP/Mg2+ pump responsible for the sequestering of neurotransmitters into storage vesicles located in the presynaptic neuron. The neurotransmitters that are not sequestered in the storage vesicle are readily metabolized by monoamine oxidase[MAO] causing a reduction in catecholamines[12, 14].
Some common adverse reactions of reserpine include dizziness, feeling sleepy, dry mouth, headache, muscle pain, stuff nose, upset stomach or throwing up, loose stools, anxiety, weight gain and nosebleed[15, 16]. More severe adverse reactions could occur as allergic reactions(such as rash, hives, itching, red, swollen, blistered with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat), chest pain or pressure, low mood(nervousness, suicidal mood, emotional ups and downs and anxiety), enlarged breasts, breast soreness, bad dreams, not hungry, swelling, lowered interest in sex, hearing loss, shortness of breath, trouble controlling body movements, pain when passing urine.
Warning and precautions
Patients of the following conditions should be disabled: being allergic, depression history, a history of suicidal thought, a stomach ulcer, ulcerative colitis and who are subjecting to treatment with electroconvulsive therapy. Patients should also seek advice from the doctors if he/she has gallstones, kidney disease, or a history of stomach problems or slow digestion, plan or has already become pregnant. Since reserpine can pass into breast milk and may do harm to a nursing baby, breast-feed is not allowed during taking this drug. Reserpine is only allowed for use in people older than 18 years old.
2. Doyle, A. E., E. G. Mcqueen, and F. H. Smirk. "Treatment of hypertension with reserpine, with reserpine in combination with pentapyrrolidinium, and with reserpine in combination with Veratrum alkaloids." Circulation11.2(1955]:170.
3. Hughes, W. M., E. Dennis, and J. H. Moyer. "Treatment of hypertension with oral reserpine alone and in combination with hydralazine or hexamethonium. " American Journal of the Medical Sciences229.2(1955]:121-134.
4. The Columbia Encyclopedia, Sixth Edition. Copyright © 2001-05 Columbia University Press.
5. Kurland, A. A. "Comparison of chlorpromazine and reserpine in treatment of schizophrenia; a study of four hundred cases. " A.m.a.archives of Neurology & Psychiatry 75.5(1956]:510-513.
6. Braun, M. "Reserpine as a therapeutic agent in schizophrenia. " American Journal of Psychiatry 116.3(1960]:744.
7. Shamon SD, Perez MI. "Blood pressure lowering efficacy of reserpine for primary hypertension". Cochrane Database of Systematic Reviews. 4: CD007655.
8. Chobanian AV, Bakris GL, Black HR, et al.. "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report". JAMA. 289: 2560–72.
9. Sharma, V. K., Harik, S. I., Ganapathi, M., Busto, R., & Banerjee, S. P.. Locus ceruleus lesion and chronic reserpine treatment: effect on adrenergic and cholinergic receptors in cerebral cortex and hippocampus. Experimental Neurology, 65(3], 685-690.
11. Sharaf ElDin, M. M., et al. "Validated liquid chromatography-tandem mass spectrometry method for simultaneous determination of clopamide, reserpine and dihydroergotoxine: Application to pharmacokinetics in human plasma. " Journal of Pharmaceutical & Biomedical Analysis125(2016]:236-244.
12. Tsunoda, I.. A study on hypertension effects of reserpine and monoamine oxidase inhibitors on blood pressure and blood plasma catecholamines. Jpn J Nephrol, 7(3], 361-371.
13. Ahmed, N. A., Radwan, N. M., Al-Zahaby, A. S., & Abd el-Salam, M. M.. Reserpine effects on neurotransmitters in chick heart during growth. Journal of Physiology Paris, 91(2], 81.
14. Häggendal, J., & Malmfors, T.. The effect of nerve stimulation on catecholamines taken up in adrenergic nerves after reserpine pretreatment. Acta Physiologica, 75(1-2], 33-38.
15. AJ Giannini, HR Black. Psychiatric, Psychogenic, and Somatopsychic Disorders Handbook. Garden City, NY. Medical Examination Publishing, 1978. Pg. 233. ISBN 0-87488-596-5.
Reserpine causes release of norepinephrine, dopamine, and serotonin at neuronal termini. It weakens the intracellular uptake of biogenic amines and decreases the ability to store them in vesicles.
off-white crystalline powder
Reserpine is a white to pale buff to slightly yellow crystalline substance that darkens on exposure to light.
Appearance: crystalline powder, colorless to yellowish brown, darker in case of light. Solubility: soluble in chloroform, slightly soluble in acetone, and almost insoluble in water, methanol, ethanol, or ether. Melting point: 264–265 °C. Specific optical rotation: ?117.7°.
In 1931, Indian scholar Sen discovered Indian Rauvolfia have the antihypertensive
and antipsychotic effects. The following studies in medicinal chemistry and pharmacology
found that the main active ingredient is reserpine and clarified th mechanism of lowering blood pressure. In 1952, reserpine was first isolated and won
an important status in treating hypertension and neurological and psychiatric disorders
because of its remarkable physiological attributes. The structure analysis of
reserpine peaked in 1955.The total synthesis of reserpine is completed in 1956.
There are no effective antihypertensive drugs in clinic at the initial stage in our country, and the reserpine imported from India was scarce and expensive, which could not meet the urgent needs of patients. In 1958, the Bureau of Drug Administration of Ministry of Health presided over the work of identifying the total alkaloids in Rauvolfia and approved the first Chinese antihypertensive drug commercially named “Verticil”. Large scales of studies about Chinese Rauvolfia as well as the numerous participants promote the rapid progress of natural medicine. It can be taken as the earliest study in plant medicine since the founding of China, providing valuable experience to our later studies.
Reserpine occurs in the roots of Rauwolfiaserpentina and other Rauwolfia species, suchas R. micrantha, R. canescens, and R. vomitoria Hook. It is used therapeutically as anantihypertensive agent and a tranquilizer. Itsuse has been reduced significantly because oftoxic side effects.
An indole alkaloid found in Rauwolfia serpentina. Inhibits vesicular uptake of catecholamines and serotonin. Reserpine is reasonably anticipated to be a human carcinogen. Antihypertensive.
An inhibitor of transport of biogenic amines into adrenal chromaffin granules
ChEBI: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria.
Rau-Sed (Bristol-Myers Squibb); Sandril (Lilly); Serpasil (Novartis).
Reserpine (Serpasil) is the prototypical drug interfering
with norepinephrine storage. Reserpine lowers blood
pressure by reducing norepinephrine concentrations in
the noradrenergic nerves in such a way that less norepinephrine
is released during neuron activation.
Reserpine does not interfere with the release process
per se as does guanethidine.
Reserpine also interferes with the neuronal storage of a variety of central transmitter amines such that significant depletion of norepinephrine, dopamine, and 5- hydroxytryptamine (serotonin) occurs. This central transmitter depletion is responsible for the sedation and other CNS side effects associated with reserpine therapy. The depletion of brain amines also may contribute to the antihypertensive effects of reserpine.
Reserpine (Serpasil, Reserpoid, Rau-Sed, Sandril) is a white to light yellow, crystalline alkaloid,practically insoluble in water, obtained from various speciesof Rauwolfia. In common with other compounds with anindole nucleus, it is susceptible to decomposition by lightand oxidation, especially when in solution. In the dry state,discoloration occurs rapidly when reserpine is exposed tolight, but the loss in potency is usually small. In solution,reserpine may break down with no appreciable color changewhen exposed to light, especially in clear glass containers;thus, color change cannot be used as an index of the amountof decomposition.
Reserpine, a prototypicaland historically important drug, is an indole alkaloid obtainedfrom the root of Rauwolfia serpentina found in India.As is typical of many indole alkaloids, reserpine is susceptibleto decomposition by light and oxidation. Reserpine isextensively metabolized through hydrolysis of the esterfunction at position and yields methyl reserpate and3,4,5-trimethoxybenzoic acid. It not only depletes the vesiclestorage of NE in sympathetic neurons in PNS, neuronsof the CNS, and E in the adrenal medulla, but also depletesthe storage of serotonin and DA in their respective neuronsin the brain. Reserpine binds extremely tightly with andblocks VMAT that transports NE and other biogenic aminesfrom the cytoplasm into the storage vesicles. Thus in sympatheticneurons, NE, which normally is transported into thestorage vesicles, is instead metabolized by mitochondrialMAO in the cytoplasm. In addition, there is a gradual loss ofvesicle-stored NE as it is used up by release resulting fromsympathetic nerve activity so that the storage vesicles eventuallybecome dysfunctional. The end result is a depletion ofNE in the sympathetic neuron. Analogous effects are seen inthe adrenal medulla with E and with 5-HT in serotonergicneurons.
White or cream to slightly yellow crystals or crystalline powder. Odorless with a bitter taste.
Air & Water Reactions
Insoluble in water. Reacts slowly with air and water. Darkens slowly on exposure to light.
Reserpine is a weak base and can form salts with strong acids. Incompatible with oxidizing agents and reducing agents.
Reserpine produces sedative, hypotensive,
LD50 value, intraperitoneal (mice): 5 mg/kg
LD50 value, oral (mice): 200 mg/kgand tranquilizing effects. This is due to itsactions of causing depletion of monoaminesfrom presynaptic nerve terminals in central and peripheral nervous systems. Theadverse side effects are drowsiness, nightmare, depression, excessive salivation, nausea, diarrhea, increased gastric secretion,abdominal cramps, and hypotension.
Flash point data for Reserpine are not available; however, Reserpine is probably combustible.
Binds the vesicular monoamine transporter (VMAT2) and inhibits transport of biogenic amines into adrenal chromaffin granules and synaptic vesicles. Causes depletion of biogenic amine stores. Antihypertensive and antipsychotic.
Mechanism of action
Reserpine acts to replace and deplete the adrenergic neurons of their stores of norepinephrine by inhibiting the active transport Mg-ATPase responsible for sequestering norepinephrine and dopamine within the storage vesicles. The norepinephrine and dopamine that are not sequestered in vesicles are destroyed by MAO. As a result, the storage vesicles contain little neurotransmitter, adrenergic transmission is dramatically inhibited, and sympathetic tone is decreased, leading to vasodilation. Reserpine has the same effect on epinephrine storage in the adrenal medulla. Reserpine readily enters the CNS, where it also depletes the stores of norepinephrine and serotonin. The CNS neurotransmitter depletion led to the use of reserpine in treating certain mental illnesses.
Limited information is available regarding the pharmacokinetics of reserpine. Peak blood concentrations for reserpine occur within 2 hours following oral administration, and the full effects for reserpine usually are delayed for at least 2 to 3 weeks. Both CNS and cardiovascular effects may persist for several days to several weeks after chronic oral therapy is discontinued. Reserpine appears to be widely distributed in body tissues, especially adipose tissue; crosses the blood-brain barrier and the placenta; and is distributed into milk. The elimination of reserpine appears to be biphasic, with a plasma half-life averaging 4.5 hours during the first phase and approximately 11.3 days during the second phase. Reserpine is metabolized to unidentified inactive compounds. Unchanged reserpine and its metabolites are excreted slowly in urine and feces, with an average of 60% reserpine recovered in feces within 96 hours after oral administration of 0.25 mg of radiolabeled reserpine.
Reserpine causes a breakdown of norepinephrine, dopamine, and serotonin in neuron endings. It weakens intracellular uptake of biogenic amines and reduces the ability if storing them in vesicles. It is possible that reserpine acts on membrane vesicles, irreversibly inhibiting ATP-Mg2 (adenosinetriphosphate) requiring process that is responsible for the uptake of biogenic amines in interneuronal vesicles. Breakdown of catecholamines is expressed by a decreased number of intraneuronal serotonin and dopamine.
Reserpine is effective orally and parenterally for thetreatment of hypertension. After a single intravenous dose,the onset of antihypertensive action usually begins in about1 hour. After intramuscular injection, the maximumeffect occurs within approximately 4 hours and lasts about10 hours. When it is given orally, the maximum effectoccurs within about 2 weeks and may persist up to 4 weeksafter the final dose. When used in conjunction with otherhypotensive drugs in the treatment of severe hypertension,the daily dose varies from 100 to 250μg.
When reserpine is given orally, its maximum effect is seenafter a couple of weeks. A sustained effect up to severalweeks is seen after the last dose has been given. This isbecause the tight binding of reserpine to storage vesicles continuesfor a prolonged time, and recovery of sympatheticfunction requires synthesis of new vesicles over a period ofdays to weeks after discontinuation of the drug. Most adverseeffects of reserpine (log P＝4.37) are caused by CNS effectsbecause it readily enters the CNS. Sedation and inability toconcentrate or perform complex tasks are the most commonadverse effects. More serious is the occasional psychoticdepression that can lead to suicide, which support monoaminetheory of pathology of depression. Agents with fewer sideeffects have largely replaced reserpine in clinical use.
The most troublesome untoward effects of treatment
with reserpine involve the CNS. Sedation and depression
are the most common, although nightmares
and thoughts of suicide also occur. Reserpine treatment,
therefore, is contraindicated in patients with a history
of severe depression. The occasional report of reserpine-
induced extrapyramidal symptoms, which are
similar to those seen in patients with Parkinson’ s disease,
is believed to be a result of dopamine depletion
from neurons in the CNS.
Peripheral nervous system side effects are the result of a reserpine-induced reduction of sympathetic function and unopposed parasympathetic activity; symptoms include nasal congestion, postural hypotension, diarrhea, bradycardia, increased gastric secretion, and occasionally impotence. Because of the increased gastric secretion, reserpine is contraindicated for patients with peptic ulcer. In patients with little cardiac reserve, reserpine must be administered with caution because of its ability to interfere with sympathetic stimulation of the heart.
Confirmed human carcinogen producing tumors of the sh and brain. Poison by ingestion, intravenous, subcutaneous, and intraperitoneal routes. Mutation data reported. An experimental teratogen. Human and experimental reproductive effects by ingestion: sullbirth, reduced viability, and other neonatal measures or effects. In humans, 0.014 mg/kg causes psychotropic effects. A medicine with side effects. Used as an addltive permitted in the feed and drinking water of animals and/or for the treatment of food-producing animals. Also permitted in food for human consumption. A sedative. When heated to decomposition it emits toxic fumes of NOx.
Reserpine is methyl ester 2α,11-dimethoxy-3-(3,4,5-trimethoxybenzoyloxy)- yohimban-1-carboxylic acid (12.3.1). Reserpine is one of the alkaloids isolated from a perennial shrub of the Rauwolfia family [67–72]. It can also be synthesized [73–76].
Reserpine, a pharmaceutical, is a natu- rally occurring substance that is isolated from the roots of the plant rauwolfia serpentina. Insoluble in water. Reserpine is used as a hypertensive for humans and ani- mals; tranquilizer, and sedative. Permitted for use as an additive in food for human consumption, and the feed and drinking water of food-producing animals.
Reserpine is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
Reserpine is a naturally occurring alkaloid produced by several members of genus Rauwolfia, indigenous to India, Burma, Malaysia, Thailand, Nepal, and Indonesia. The release of reserpine to the environment through several waste streams is possible due to the manufacture of reserpine and/or excretion following therapeutic use. It has a pKb of 6.6 and is expected to be in a partially protonated state in the environment. Reserpine released into air at ambient temperature and pressure exists only in the particulate phase and is removed from the atmosphere by wet and dry deposition. Reserpine released to soil is available in oral dosage forms in combinations with hydralazine (a vasodilator) and/or hydrochlorothiazide (a thiazide diuretic). Occupational exposure would be expected to occur through inhalation or dermal contact.
UN1544 Alkaloids, solid, n.o.s. or Alkaloid salts, solid, Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required. UN3077 Environmentally haz- ardous substances, solid, n.o.s., Hazard class: 9; Labels: 9- Miscellaneous hazardous material, Technical Name Required.
Crystallise reserpine from aqueous Me2CO or Et2O. [Woodward et al. Tertrahedron 2 155 1958, Beilstein 25 III/IV 1319.]
The pharmacology and toxicology of reserpine stem from the same mechanism of action. Reserpine binds tightly and irreversibly to the adrenergic storage vesicles, inhibits the vesicular monoamine transporter 2 (VMAT2), and prevents the concentration of monogenic amines norepinephrine (NE) and dopamine (DA) in the nerve terminals. The neurotransmitters NE and DA are metabolized by monoamine oxidases and catechol-O-methyl transferases in the cytoplasm, depleted from nerve terminals, and are unavailable for release into the synapse upon nerve stimulation. Sympatholytic activity in peripheral adrenergic neurons leads to decrease in peripheral vascular resistance, cardiac output, and blood pressure and in the central adrenergic neurons, causes central nervous system (CNS) depression. The action is long lasting because replenishing the storage vesicles with VMAT and neurotransmitters requires new protein synthesis and may take days to weeks after discontinuation of reserpine.
A weak acid; keep away from bases. Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoa- cids, epoxides, and strong reducing agents such as hydri- deds and active metals. Compounds of the carboxyl group react with all bases, both inorganic and organic (i.e., amines) releasing substantial heat, water, and a salt that may be harmful. Incompatible with arsenic compounds (releases hydrogen cyanide gas), diazo compounds, dithio- carbamates, isocyanates, mercaptans, nitrides, sulfides (releasing heat, toxic, and possibly flammable gases),thiosulfates, and dithionites (releasing hydrogen sulfate and oxides of sulfur).
It is inappropriate and possi- bly dangerous to the environment to dispose of expired or waste drugs and pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quanti- ties of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double-bagged in plastic, discard in trash. Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator. Consult with environmental regula- tory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (≥100 kg/ mo) must conform with EPA regulations governing storage, transportation, treatment, and waste disposal.
Muller, Schlittler, Bein., Experientia, 8,338 (1952)
Woodward et al., Tetrahedron, 2, 1 (1958)
Jilek e t aI., Collect. Czech. Chem. Commun., 26, 687 (1961)
Hakkesteegt., Pharm. Weekbl., 105,829 (1970)
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