Reserpin

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Gefahrenhinweise

  H302：Gesundheitsschädlich bei Verschlucken.

  H336：Kann Schläfrigkeit und Benommenheit verursachen.

  H351：Kann vermutlich Krebs verursachen.

• Sicherheit

  P201：Vor Gebrauch besondere Anweisungen einholen.

  P308+P313：BEI Exposition oder falls betroffen: Ärztlichen Rat einholen/ärztliche Hilfe hinzuziehen.

Reserpine Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R22:Gesundheitsschädlich beim Verschlucken.
  R67:Dämpfe können Schläfrigkeit und Benommenheit verursachen.
  R36:Reizt die Augen.
  R10:Entzündlich.

• S-Sätze Betriebsanweisung:

  S22:Staub nicht einatmen.
  S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.

• Beschreibung

  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.

• Beschreibung

  Reserpine is an alkaloid isolated from dried roots of R. serpentine, which is used in traditional Indian medicine. Reserpine irreversibly inhibits both human isoforms of vesicular monoamine transporter, VMAT1 and VMAT2 (K_is = 34 and 12 nM, respectively). As this leads to metabolism of monoamines, reserpine is used to experimentally deplete monoamines in animals. Reserpine also inhibits the multidrug resistance protein P-glycoprotein (IC₅₀ = 0.5 μM).

• Chemische Eigenschaften

  Reserpine is a white to pale buff to slightly yellow crystalline substance that darkens on exposure to light.

• Chemische Eigenschaften

  off-white crystalline powder

• Physikalische Eigenschaften

  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°.

• History

  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.

• Verwenden

  An indole alkaloid found in Rauwolfia serpentina. Inhibits vesicular uptake of catecholamines and serotonin. Reserpine is reasonably anticipated to be a human carcinogen. Antihypertensive.

• Verwenden

  An inhibitor of transport of biogenic amines into adrenal chromaffin granules

• Verwenden

  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.

• Definition

  ChEBI: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria.

• Trademarks

  Rau-Sed (Bristol-Myers Squibb); Sandril (Lilly); Serpasil (Novartis).

• Biologische Funktion

  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.

• Allgemeine Beschreibung

  White or cream to slightly yellow crystals or crystalline powder. Odorless with a bitter taste.

• Allgemeine Beschreibung

  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.

• Allgemeine Beschreibung

  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.

• Air & Water Reaktionen

  Insoluble in water. Reacts slowly with air and water. Darkens slowly on exposure to light.

• Reaktivität anzeigen

  Reserpine is a weak base and can form salts with strong acids. Incompatible with oxidizing agents and reducing agents.

• Hazard

  Questionable carcinogen.

• Health Hazard

  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.

• Brandgefahr

  Flash point data for Reserpine are not available; however, Reserpine is probably combustible.

• Biologische Aktivität

  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.

• Biochem/physiol Actions

  Reserpine is used to treat hypertensive pregnancy difficulties. This drug is also considered as antipsychotic and antihypertensive, to regulate high blood pressure.

• 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.

• Pharmakokinetik

  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.

• Pharmakologie

  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.

• Clinical Use

  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.

• Clinical Use

  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.

• Nebenwirkungen

  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.

• Sicherheitsprofil

  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.

• Synthese

  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].

• mögliche Exposition

  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.

• target

  Caspase | SOD | Beta Amyloid | NMDAR

• Erste Hilfe

  Skin Contact: Flood all areas of body that havecontacted the substance with water. Do not wait to removecontaminated clothing; do it under the water stream. Usesoap to help assure removal. Isolate contaminated clothingwhen removed to prevent contact by others.Eye Contact: Remove any contact lenses at once.Immediately flush eyes well with copious quantities ofwater or normal saline for at least 20-30 min. Seek medicalattention.Inhalation: Leave contaminated area immediately; breathefresh air. Proper respiratory protection must be supplied toany rescuers. If coughing, difficult breathing, or any othersymptoms develop, seek medical attention at once, even ifsymptoms develop many hours after exposure.Ingestion: Contact a physician, hospital, or poison center atonce. If the victim is unconscious or convulsing, do notinduce vomiting or give anything by mouth. Assure that thepatient’s airway is open and lay him on his side with hishead lower than this body and transport immediately to amedical facility. If conscious and not convulsing, give aglass of water to dilute the substance. Vomiting should notbe induced without a physician’s advice.

• Carcinogenicity

  Reserpine is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.

• Environmental Fate

  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.

• Lager

  Room temperature

• Versand/Shipping

  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.

• läuterung methode

  Crystallise reserpine from aqueous Me2CO or Et2O. [Woodward et al. Tertrahedron 2 155 1958, Beilstein 25 III/IV 1319.]

• Toxicity evaluation

  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.

• Inkompatibilitäten

  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).

• Waste disposal

  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.

• Einzelnachweise

  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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