레세르핀

White or pale buff to slightly yellowish powder

Long prisms from dil acetone

less than 1 mg/mL at 72 °F (NTP, 1992)

Freely sol in chloroform (approx. 1 g/6 ml), methylene chloride, glacial acetic acid; sol in benzene, ethyl acetate; slightly sol in acetone, methanol, alcohol (1 g/1800 ml), ether, and in aq solns of acetic and citric acids.

In water, 73 mg/l @ 30 °C

1.13e-02 g/L

Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

MELTING POINT: 264-265 °C (DECOMP)

When heated to decomposition it emits toxic fumes of /nitrogen oxides/.

507 to 509 °F (decomposes) (NTP, 1992)

264.5 °C

264.5 °C

Specific optical rotation: -118 deg @ 23 °C/D (c= 1 in chloroform), -168 deg @ 26 °C/D (c= 0.624 in dimethylformamide), -164 deg @ 26 °C/D (c= 0.96 in pyridine); max absorption (chloroform): 216 nm, 267 nm, 295 nm (log e= 61,700; 17,000; 10,200)

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 204 reports by companies from 9 notifications to the ECHA C&L Inventory.

Hazard Traits - Carcinogenicity

S - indicates a substance that is identified in a final Significant New Use Rule.

Reserpine: Does not have an individual approval but may be used under an appropriate group standard

SYMPTOMS: Symptoms of exposure to this compound may include lowered blood pressure, sedation, bradycardia, drowsiness, nasal congestion, weight gain and severe mental depression which may lead to suicide. Other symptoms include lethargy, vertigo, gastrointestinal upset, dyspnea, flushing and parkinsonism. It can cause nightmares and an increase in gastrointestinal tone and motility with abdominal cramps and diarrhea. It can also cause insomnia, cardiotoxic effects (such as premature ventricular contractions and other arrhythmias, possible sensitization to digitalis, fluid retention and congestive failure), fatigue, weakness, excitement, irrational behavior and sodium retention edema. Exposure can cause dryness of the mouth, pruritus and skin rashes, angina-like syndrome, blurred vision, breast engorgement and galactorrhea, impotence, epistaxis, difficulty in micturition, purpura, bronchospasm, thrombocytopenia, effects on the endocrine system, interference with color vision, hematemesis, systemic lupus erythematosus and breast cancer. Exposure can also cause an increase in appetite, anxiety, headache and disturbance of ejaculation. Other symptoms include nausea with anorexia, excessive salivation, reduction in emotional tension, sleepiness, dizziness, apathy, confusion, restlessness, hallucinations, vomiting, excessive secretory and motor activity of the stomach (which may eventually lead to the formation of peptic ulcer with pain, hemorrhage and perforation), blockade of peripheral adrenergic nerves (which may cause peripheral vasodilatation), motor disturbances (apparently of the extrapyramidal system characterized by stiffness with aching pain in the legs, tremors and various types of dystonia and catatonia), hypothermia, cardiovascular collapse and coma with blushing. Chronic exposure may cause hormonal disturbances, notably mild feminization of adult males with gynecomastia and lactation. Anginal pain and extrasystoles have occurred. Psychotropic effects have also occurred. Eyes may appear slightly flushed due to the dilation of conjunctival blood vessels. Lacrimation, slight miosis and ocular spasms may occur. Eye effects also include conjunctival hyperemia. This chemical may cause serious respiratory problems in infants born to mothers exposed to it during pregnancy. Intramuscular or intravenous injection may cause postural hypotension and duodenal ulcers.

Drug products withdrawn or removed from the market for reasons of safety or effectiveness. Reserpine: All oral dosage form drug products containing more than 1 milligram of reserpine.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

DHEW/NCI; Bioassay of Reserpine for Possible Carcinogenicity (1980) Technical Rpt Series No. 193 DHEW Pub No. (NIH) 80-1749

National Toxicology Program. Eleventh Report on Carcinogens (2005). The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Reserpine (50-55-5) is listed as reasonably anticipated to be a human carcinogen.[Available from, as of July 31, 2009: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s158rese.pdf]

U200; As stipulated in 40 CFR 261.33, when reserpine, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SMALL SPILLS AND LEAKAGE: If a spill of this chemical occurs, FIRST REMOVE ALL SOURCES OF IGNITION, then you should dampen the solid spill material with acetone and transfer the dampened material to a suitable container. Use absorbent paper dampened with acetone to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with acetone followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids. /From table/

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). (NTP, 1992)

NINE MALE WISTAR RATS GIVEN 16 MG/KG OF DIET WERE PROTECTED AGAINST CARCINOGENIC EFFECTS OF NITROSODIETHYLAMINE (50 MG/L IN THE DRINKING-WATER). FIFTEEN DAILY SC INJECTIONS OF RESERPINE IN RATS FROM AGE OF 50 DAYS, FOLLOWED AT AGE OF 55 DAYS BY SINGLE IV INJECTION OF DIMETHYLBENZ[A]ANTHRACENE, RESULTED IN INHIBITORY ACTION ON MAMMARY TUMOR PRODUCTION OF DIMETHYLBENZ[A]ANTHRACENE ALONE (81% VS 100%).

POTENTIATES PARATHION & CARBARYL TOXICITY IN RATS.

/Reserpine/ may sensitize anesthetics and interfere with cardiovascular adjustments during surgery.

When Rauwolfia alkaloids are administered with diuretics or other hypotensive agents, the hypotensive effects of the alkaloids may be increased. /Rauwolfia alkaloids/

For more Interactions (Complete) data for RESERPINE (13 total), please visit the HSDB record page.

Serum aminotransferase elevations during reserpine therapy are uncommon, but specific rates of such elevations in comparison to placebo treatment have not been reported. Despite many decades of use, reserpine has been implicated in few instances of clinically apparent acute liver injury, and none of them were particularly convincing. Published cases were marked by jaundice and abdominal pain arising a year after starting reserpine, but in combination with other known hepatotoxic agents (dihydrazine, phenobarbital, quinidine). The few cases that have been reported were self-limiting and resolved within a few months of stopping therapy. The last case of suspected reserpine associated liver injury was published more than 50 years ago.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2.70X10+6(SRC), determined from a structure estimation method(2), indicates that reserpine is expected to be immobile in soil(SRC). The pKb of reserpine is 6.6(5), indicating that this compound will exist partially in the protonated form in the environment and cations generally adsorb to organic carbon and clay more strongly than their neutral counterparts. Volatilization of reserpine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 5.4X10-23 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Reserpine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.5X10-16 mm Hg(SRC), determined from a fragment constant method(4).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2.70X10+6(SRC), determined from an estimation method(2), indicates that reserpine is expected to adsorb to suspended solids and sediment in water(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 5.4X10-23 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). A pKb of 6.6(7) indicates reserpine will exist partially in the protonated form in aqueous environments and cations are not expected to volatilize from water surfaces. A hydrolysis half-life was reported to be 1.7 yrs at pH 7 and 25 °C(8). According to a classification scheme(5), an estimated BCF of 72(SRC), from an estimated log Kow of 3.3(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is moderate.

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), reserpine, which has an estimated vapor pressure of 4.5X10-16 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate- phase reserpine may be removed from the air by wet and dry deposition(SRC). Reserpine is sensitive to oxidation and hydrolysis(3).

IDENTIFICATION: Reserpine is an antihypertensive agent. Origin of the substance: An alkaloid from the roots of certain species of Rauwolfia, usually Rauwolfia serpintina or R. vomitoria. Reserpine can also be synthesized. Color: White or pale buff to slightly yellow colored. It is insoluble in water, freely soluble in chloroform and acetic acid, and very slightly soluble in alcohol and ether. Bioavailability: The reported bioavailability after oral ingestion is approximately 50%. Indications: Description: Hypertension; Raynaud's phenomenon; possibly for prevention of attacks of familial Mediterranean fever. Possibly for treatment of thyroid storm not responsive to standard therapy. HUMAN EXPOSURE: Main risks and target organs: The main risks associated with reserpine poisoning are central nervous system depression, the development of psychiatric depression, cardiovascular toxicity, and gastrointestinal irritation. The main target organs are the central nervous system, cardiovascular system, and gastrointestinal tract. Summary of clinical effects: The clinical effects include sedation and lethargy, which can rarely progress to coma, and gastrointestinal irritation which includes nausea, vomiting, and abdominal cramping. Gastrointestinal irritation can be severe and result in ulceration, perforation, and hemorrhage. Psychiatric depression can be severe and lead to suicidal thoughts and there can be nightmares, and vertigo. Cardiovascular effects include hypotension and bradycardia. Nasal congestion and flushing are also frequent. Hypothermia has also been described. These effects are generally more common with poisonings. The most commonly reported effects were facial flushing, lethargy which rarely progressed to coma, hypotension and bradycardia. Death has been described from hypotension in two patients. Contraindications: Absolute: Pregnancy, psychiatric depression, active peptic ulcer disease; ulcerative colitis; Parkinson's disease; pheochromocytoma and hypersensitivity to any rauwolfia alkaloid Relative contraindications where the use of reserpine should be undertaken with caution and started with lower doses: Elderly patients, cardiac arrhythmias; myocardial infarction; renal insufficiency and asthma. Routes of entry: Oral: The most common route of administration and poisoning. Parenteral: Intramuscular injection has been used for the urgent treatment of hypertension. Intra-arterial injection has been described in Raynaud's syndrome, but appears to be ineffective. Absorption by route of exposure: The reported bioavailability is approximately 50% to 70% after oral ingestion. Absorption is relatively rapid, with peak concentrations achieved approximately 1 to 2 hours after administration of an oral solution. Slower absorption, with peak concentrations at 2 to 4 hours has also been reported. Distribution by route of exposure: The volume of distribution has not been reported. It is widely distributed into the brain, liver, spleen, kidney, and adipose tissue. Reserpine binds to red blood cells and in the peripheral neuron at its site of action. It is reported not to bind to plasma protein. Reserpine crosses the placental barrier, and is found in breast milk. An initial half-life of distribution of approximately 4 to 5 hours is observed after oral administration. Biological half-life by route of exposure: Reserpine can be described using a two compartmental pharmacokinetic model. The elimination half-life ranges from 45 to 168 hours in plasma. Because of binding to red blood cells, the terminal elimination half-life is longer when whole blood levels is measured, and has been reported to be 386 hours. The half-life is longer in patients with renal insufficiency. The elimination half-life was significantly prolonged in patients with creatinine clearance values of less than 10 mL/min. Metabolism: Hepatic metabolism accounts for less than 50% of the elimination of reserpine, with the remainder being eliminated in the feces, and some unmetabolized reserpine and metabolites being eliminated in the urine. In man, metabolites are methylreserpate and trimethoxybenzoic acid. Metabolism may be more important with intramuscular administration. Elimination by route of exposure: The elimination of reserpine and its metabolites in the feces ranges from 30% after intramuscular administration to approximately 60% after oral administration, primarily as unmetabolized reserpine, over a 4 day period. Over the same time period approximately 8% of the administered dose was recovered in the urine, primarily as the trimethoxybenzoic acid metabolite. Pharmacology and toxicology: Mode of action: Toxicodynamics: The mechanism of reserpine's toxic effects is similar to the mechanism of it's pharmacologic effects. Reserpine inhibits normal sympathetic activity in both the CNS and peripheral nervous system by binding to catecholamine storage vesicles. This prevents the normal storage of catecholamines and serotonin in the nerve cell, with the result being catecholamine depletion. Reserpine has also been described as inhibiting catecholamine synthesis by blocking the uptake of dopamine into the storage vesicle. Pharmacodynamics: Reserpine inhibits normal sympathetic activity by decreasing the storage of catecholamines at the pre-synaptic, CNS, and peripheral neuron. Reserpine binds to the storage vesicles, causing catecholamines to leak into the synapse so that they are not available for release when the pre-synaptic neuron is stimulated. The process appears to affect serotonin storage in a similar manner. These actions result in a reduction in both cardiac output and peripheral vascular resistance with long term therapy, which takes approximately 3 weeks to develop after the initiation of therapy. Heart rate and renin concentrations decrease, and there is sodium and water retention. Human data: Adults: There are few reported cases of reserpine poisoning in adult patients. In a series of 151 cases reported from the United States from 1959 to 1960 only 4% were adults. Nausea, vomiting, hypotension, sedation, and coma were described in these patients. Psychiatric depression is historically the most important adverse effect associated with the chronic administration of reserpine for the treatment of hypertension. The depression is most common with higher daily doses, and the frequency is significantly decreased when the dose is lower. The depression is often severe, can occur in patients without a prior history of depressive illness, and may last for months after reserpine is discontinued. Children: Most of the reported cases of reserpine poisoning have been in children. One hundred forty two of the 151 cases of rauwolfia poisoning were in children less than 13 years of age. Approximately 40% of the cases had some symptoms, Mild CNS depression such as lethargy or sedation was the most common symptom, and facial flushing the next most common. Hospitalization for toxicity was needed in 24 of the 142 pediatric cases. Nausea, vomiting, hypotension and vertigo were also described. Individual cases of toxicity include information about potential doses of reserpine ingested and the time course of toxicity. A 20 month old male who ingested reserpine had symptoms of lethargy, flushing, rapid pulse rate and slowed respiration. Within 21 hours the symptoms had primarily resolved without any specific therapy other than a cathartic. A mild leukocytosis resolved within 2 weeks. Three cases of reserpine ingestion in children between 30 months and 4 years of age, who ingested large doses of reserpine (2 cases), and an unknown dose (1 case), demonstrated a wide range of toxicity. All cases had some lethargy and CNS depression which progressed to coma. Bradycardia and hypothermia was also documented in all cases, while the youngest child also had an episode of hypertension and tachycardia starting about 10 hours after ingestion. Carcinogenicity: There does not appear to be an association between reserpine administration and cancer. Teratogenicity: In 48 cases of mothers who had taken reserpine during their first trimester of pregnancy, the incidence of birth defects was 8%, higher than expected, although no major types of malformations were seen. There was no increased risk of birth defects in women who ingested reserpine at any time during their pregnancy. Interactions: The following drugs have been reported to interact with reserpine: Alcohol and CNS depressant drugs: increased sedation Nonsteroidal anti-inflammatory drugs: increased risk of gastric irritation Drugs with antimuscarinic actions: increased gastric acid secretion Beta-adrenergic blocking agents: additive beta adrenergic blockade Bromocriptine: increased serum prolactin and decreased bromocriptine activity Digitalis glycosides: possible increase in bradycardia and arrhythmias Quinidine: possible increase in arrhythmias Estrogens: decrease antihypertensive effects of reserpine Drugs causing extrapyramidal adverse effects: potentiate extrapyramidal activity Antihypertensive agents: hypotension Levodopa: decreased efficacy of levodopa Monoamine oxidase inhibitors: increased CNS depression or increased blood pressure and CNS stimulation Sympathomimetics: decreased effects of reserpine Main adverse effects: The main adverse effects described with the therapeutic administration of reserpine include lethargy and sedation, psychiatric depression, hypotension, nausea, vomiting, abdominal cramping, gastric ulceration, nightmares or vivid dreams, bradycardia, and bronchospasm (in asthmatics) Much less common are symptoms of skin rash or itching, Parkinsonian effects, and thrombocytopenia. Adverse effects are more common with daily doses of reserpine of 0.5 mg or greater. The lethargy and sedation is more common when other CNS depressant drugs are being used concurrently. Adverse reactions were reported in 26 of 231 hospitalized patients who received reserpine. Three reactions after intramuscular reserpine doses of 0.5 mg or greater were considered life-threatening (hypotension in 2 patients, cerebral edema in 1 patient), but no deaths were attributed to reserpine. Bronchospasm has been described when reserpine is administered to asthmatics, and may be relatively common. A case of withdrawal psychosis has been described. Clinical effects: Acute poisoning: Ingestion: Poisoning with reserpine most commonly results in lethargy, sedation, and infrequently results in coma. Other effects include psychiatric depression, hypothermia, facial flushing, nausea, vomiting, abdominal cramping, and cardiovascular toxicity including hypotension and bradycardia. Parenteral exposure: After intramuscular injection of therapeutic doses of reserpine, hypotension, bronchospasm, lethargy and sedation have occurred. These effects are most commonly secondary to larger doses, and are not expected to be any different than the adverse effects associated with oral reserpine administration. Chronic poisoning: Ingestion: The development of psychiatric depression, which can be severe, and gastric ulceration and hemorrhage are the most severe adverse effects of chronic reserpine therapy. Nasal congestion, dry mouth, diarrhea, abdominal pain, lethargy, Parkinsonian features, breast enlargement, galactorrhea, impotence, sodium retention, peripheral edema, and weight gain have been reported much less commonly. Parenteral exposure: The administration of intramuscular reserpine results in adverse effects similar to those seen with oral administration. They are more commonly reported following intramuscular injection because of the larger doses administered and the increased bioavailability associated with this route. Course, prognosis, cause of death: Symptoms of toxicity develop over the first 4 hours after ingestion. Symptoms generally resolve over 18 to 24 hours. The prognosis is generally very good, and patients recover without sequelae. The psychiatric depression can take months to resolve. Two deaths following reserpine poisoning have been reported in the Russian literature. Both cases were adults who died of cardiovascular collapse and multi-organ system failure in the first few days after ingestion. Systematic description of clinical effects: Cardiovascular: Cardiovascular effects associated with reserpine poisoning are relatively uncommon, with only two cases of hypotension reported in a total of 151 patients. Bradycardia is also described, and there is one case of tachycardia and hypertension which developed approximately 10 hours after ingestion. Angina-like symptoms, and dysrhythmias are possible when reserpine is administered to patients taking a digitalis glycoside, quinidine or procainamide. Respiratory: Upper respiratory bronchospasm and nasal congestion may occur. Neurological: CNS: The most common symptoms with poisoning are lethargy and sedation, which occurred in 44% of 151 rauwolfia poisonings. Coma is much less common. A decrease in body temperature may develop. With poisonings, psychiatric depression may occur, however, it is more commonly described with chronic reserpine use. Additional CNS effects include nightmares and vivid dreams, vertigo, headache, dizziness, nervousness, anxiety, and rarely deafness. The development of extrapyramidal symptoms including dystonia and Parkinson's symptoms is reported, though it is not clear whether these develop after poisonings, or only with chronic therapy. There is a case of reserpine withdrawal psychosis which developed over 1 week after a 66 year old female ceased the daily ingestion of 3 mg of reserpine. Reserpine lowers the seizure threshold, however, clonic seizures have been described in only one case. Peripheral nervous system: The effects of reserpine on the peripheral nervous system catecholamine stores would be expected to diminish the responsiveness of the reserpine poisoned patients to indirect acting vasoconstrictors such as dopamine. Direct acting agents such as phenylephrine, metaraminol, and norepinephrine are suggested as vasoconstrictors for the treatment of hypotension which is unresponsive to intravenous fluids. Autonomic nervous system: No direct effects are described. The development of gastrointestinal ulceration is described as being due to increased gastric acid secretion which could be due to changes in autonomic nervous system function. Skeletal and smooth muscle: Gastric cramping is described. Muscle weakness can also occur. Gastrointestinal: Abdominal cramping, nausea, vomiting. Gastric ulceration and hemorrhage are less common. Urinary: Other: Painful or difficult urination is described as a rare adverse effect of chronic therapy. Endocrine and reproductive systems: Chronic therapy is associated with breast engorgement and galactorrhoea. Gynecomastia, increased prolactin concentrations, decreased libido and impotence are also potential adverse effects of chronic therapy. It is not known whether these effects occur with acute poisonings. Dermatological: Facial flushing, rashes, and pruritis. Eye, ear, nose, throat: local effects: Nasal congestion, sialorrhea, slight decrease in color vision, conjunctival injection, lacrymation, and miosis. Hematological: Thrombocytopenic purpura Immunological: Angioimmunoblastic lymphadenopathy Metabolic: Fluid and electrolyte disturbances: Sodium and water retention with the development of edema. Allergic reactions: There is cross sensitivity with reserpine among the different rauwolfia substances. Reports of allergic reactions were not identified. Special risks: The administration of reserpine at the end of pregnancy can cause nasal congestion, respiratory distress, cyanosis, poor feeding, and lethargy in the newborn infant. Reserpine is accepted therapy during breastfeeding. ANIMAL/PLANT STUDIES: Carcinogenicity: Studies in rats and mice using doses at least 100 fold greater than the usual human dose have demonstrated an increased incidence of mammary fibroadenomas, malignant tumors of the seminal vesicles, and malignant adrenal medullary tumors. Teratogenicity: Reserpine administered in large doses has been demonstrated to be teratogenic in rats and guinea pigs. Mutagenicity: Recent studies have suggested a lack of mutagenic, genotoxic, and recombinogenic effects.

Symptoms from reported cases of reserpine poisoning include hypotension, nausea, vomiting, sedation, coma, cardiovascular collapse, and death, while the latter two are uncommon.

Reserpine's mechanism of action is 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.

The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=50-55-5]

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

Using a structure estimation method based on molecular connectivity indices(1), the Koc for reserpine can be estimated to be 2.70X10+6(SRC). According to a classification scheme(2), this estimated Koc value suggests that reserpine is expected to be immobile in soil. The pKb of reserpine is 6.6(3), indicating that this compound will exist partially in the protonated form in the environment and cations generally adsorb to organic carbon and clay more strongly than their neutral counterparts.

Three children, aged 2.5 to 4 yr, ingested large doses of reserpine; 2 had taken at least 25 mg between them. Coma, with hypothermia and bradycardia developed, and the urinary excretion of catecholamines rose markedly in children, but 1 had hypertension and tachycardia. Each was treated successfully by gastric lavage, saline enemas, the application of heat during the hypothermic phase, and fluid maintenance for the first 36 hours.

... Reported pregnancy outcome from 15 women treated with reserpine. One stillborn and one pair of twins with congenital lung cysts resulted ... reported 4 malformations among the offspring of 48 women taking reserpine or other rauwolfia alkaloids during the first 4 months. In 1955 ... found nasal congestion with cyanosis, costal retraction and lethargy in newborns whose mothers were treated close to the time of parturition.

For use anytime in pregnancy, ... Malformations included: microcephaly ..., hydronephrosis ..., hydroureter ..., inguinal hernia ... . ...Reserpine crosses the placenta. Use of reserpine near term has resulted in nasal discharge, retraction, lethargy, and anorexia in the newborn. Concern over the ability or reserpine to deplete catecholamine levels has appeared.

... Drugs such as reserpine ... which supress the body's thermal regulatory center, may be more toxic at certain temperatures.

... Drugs such as reserpine ... supress the body's thermal regulatory center ...

Drug products withdrawn or removed from the market for reasons of safety or effectiveness. Reserpine: All oral dosage form drug products containing more than 1 milligram of reserpine.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

U200; As stipulated in 40 CFR 261.33, when reserpine, as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as a hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5).

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 500 lb or 2270 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

C - Cardiovascular system

QC - Cardiovascular system

Reserpine is an adrenergic blocking agent used to treat mild to moderate hypertension via the disruption of norepinephrine vesicular storage. The antihypertensive actions of Reserpine are a result of its ability to deplete catecholamines from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral resistance.

Reserpine's mechanism of action is 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.

... DEPLETES OR RELEASES SEROTONIN (5-HYDROXYTRYPTAMINE), DOPAMINE ... NOREPINEPHRINE FROM ... BRAIN & ... BODY ... DEFICIENCY OF DOPAMINE IN BRAIN ... IN STRIATUM, SUBSTANTIA NIGRA ... PALLIDUM. ... HYPOTHERMIC EFFECT ... RELATED TO SEROTONIN DEPLETION OF HYPOTHALAMIC REGION. HYPOTHALMUS CONTAINS ... HIGHEST CONCN OF SEROTONIN. ...

ANTIHYPERTENSIVE ACTION ... DERIVES FROM ADRENERGIC NEURONAL BLOCKADE CONSEQUENT TO DEPLETION OF CATECHOLAMINE-CONTAINING GRANULES OF POSTGANGLIONIC SYMPATHETIC NEURON. MECHANISM OF CENTRAL EFFECTS IS UNKNOWN. IT DEPLETES BOTH BRAIN SEROTONIN & CATECHOLAMINES.

... REPORTED TO INHIBIT GROWTH OF LEUKEMIA IN L1210 CELLS IN MALE MICE ... AND TO SUPPRESS GROWTH OF SARCOMA 37 IN MICE. ... RESERPINE DID NOT AFFECT GROWTH OF TRANSPLANTED MAMMARY ADENOCARCINOMAS IN C3H MICE. IT BLOCKS RELEASE OF PROLACTIN-INHIBITING FACTOR & THUS RAISES SERUM PROLACTIN LEVELS.

Peripheral-Acting Adrenergic Antagonist /from table/

For more Mechanism of Action (Complete) data for RESERPINE (8 total), please visit the HSDB record page.

YIELDS 3,4,5-TRIMETHOXYBENZOIC ACID IN RAT, CAT, MOUSE;

YIELDS METHYL RESERPATE IN RAT, CAT;

IDENTIFIED METABOLIC PRODUCTS ARE RESERPIC ACID, SYRINGIC ACID, & SYRINGOYL METHYL RESERPATE.

In rats, orally administered reserpine is rapidly hydrolysed to methyl reserpate; and in mice, orally or intravenously administered reserpine is metabolized to trimethoxybenzoic acid. In rats, methyl reserpate appears to be formed in the intestinal mucosa. Trimethoxybenzoic acid is rapidly eliminated in the urine of mice.

Route of Elimination: Reserpine is extensively metabolized to inactive compounds. It is slowly excreted via the urine and feces.

8B1QWR724A

RESERPINE

Established Pharmacologic Class [EPC] - Catecholamine-depleting Sympatholytic

Physiologic Effects [PE] - Decreased Sympathetic Activity

Reserpine is a Catecholamine-depleting Sympatholytic. The physiologic effect of reserpine is by means of Decreased Sympathetic Activity.

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.

Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.

Reserpine is extensively metabolized to inactive compounds. It is slowly excreted via the urine and feces.

In man, after oral admin of 0.25 mg (3)H-reserpine, tritium was rapidly absorbed into the blood, reaching a peak within 1-2 hr. Radioactivity was tightly bound to red blood cells and remained constant over a 96 hr period. ... Six percent of the dose was excreted in the urine by 24 hr, mainly as trimethoxybenzoic acid; but radioactivity was still detectable in plasma, urine, and feces 11-12 days after drug admin.

PARENTERAL ADMIN OF RESERPINE PRODUCES GREATER CONCN IN NEONATAL RAT BRAIN THAN IN ADULT ANIMALS ... PARALLELED BY GREATER DEPLETION OF NOREPINEPHRINE IN INFANT THAN IN ADULT BRAIN. THIS MAY BE DUE TO LESSER CAPACITY OF RAT NEONATES TO METABOLIZE RESERPINE ... MIGHT ALSO EXPLAIN HIGHER PLASMA & TISSUE LEVELS IN HUMAN ADULTS.

RESERPINE LEAVES BLOOD WITHIN FEW MIN AFTER IV INJECTION & ACCUMULATES IN FATTY TISSUES ... MAX CONCN IN 4-6 HR. LIVER ALSO ACCUMULATES RESERPINE. MOST OF SINGLE DOSE HAS LEFT FAT & LIVER IN 48 HR. BRAIN RETAINS ... RESERPINE & ... METABOLITES ... 5 DAYS AFTER SINGLE DOSE.

... CLAIMED TO BE ADEQUATELY ABSORBED FROM GI TRACT, BUT DIFFERENCE IN EFFICACY OF ORAL & IV DOSES RAISES DOUBTS ABOUT ADEQUACY OF ABSORPTION. ... HAS LONG LATENCY OF ONSET & PROLONGED DURATION OF ACTION.

For more Absorption, Distribution and Excretion (Complete) data for RESERPINE (8 total), please visit the HSDB record page.

Antihypertensive, central depressant, and sedative drug for both humans and animals.

Therap cat: Antihypertensive

Therap cat (Vet): Hypotensive, tranquilizer. Has been used to prevent aortic rupture in turkeys.

Foe the treatment of hypertension

Powdered Rauwolfia serpentia contains several alkaloids. Lactose, starch, or Rauwolfia serpentia containing a higher alkaloid content is added to the commercially available product so that it contains 0.15-0.20% of the reserpine-rescinnamine group alkaloids, calculated as reserpine.

(1970) 9.99X10+3 GRAMS

(1983) 4.68X10+4 g

(1984) 103 lb

(1972) PROBABLY GREATER THAN 4.54X10+5 GRAMS

(1975) PROBABLY GREATER THAN 4.54X10+5 GRAMS

Isolation from roots of Rauwolfia serpentina L Benth, Apocynaceae: Dorfman et al, Helv Chim Acta 37, 59 (1954); Schwyzer, Mueller, US patent 2,833,771 (1958 to Ciba). Structure: Dorfman et al, Loc cit; Neuss et al, J Am Chem Soc 76, 2463 (1954). ... synthesis: Woodward et al, J Am Chem Soc 78, 2023 (1956).

Reserpine (Sandril, Serpasil, others) is available in tablets that contain 0.1, 0.25 or 1.0 mg or in capsules that contain 0.5 mg

Dosage Forms- Extended-Release Capsules: 0.5 mg. Elixir: 0.2 mg/4 ml; Injection: 5 mg/2 ml, and 25 mg/10 ml; Tablets; 0.1, 0.25, 0.5, and 1 mg

Reserpine combinations: Oral tablets: 0.1 mg with hydralazine hydrochloride 25 mg: Serpasil, Apresoline, Hydrochloride #1 (with tartrazine) (Ciba); 0.1 mg with hydralazine hydrochloride 25 mg and hydrochlorothiazide 15 mg: Cherpas (Kay), HHR (Geneva Generics, Schein, Towne), Hydroserpine Plus (Zenith), Rezide (Edward), Ser-A-Gen (Goldline) Ser-Ap-Es (Ciba), Serathide (Interstate), Serpazide (Major), Tri-Hydroserpine (Rugby), Unipres (Reid-Rowell).

Reserpine combinations: Oral tablets: 0.1 mg with hydrochlorothiazide 25 mg: Serpasil, Esidrix (with tartazine) (Ciba); 0.1 mg with hydrochlorothiazide 50 mg: Serpasil, Esidrix #2 (with tartazine) (Ciba), 0.1 mg with methyclothiazide 2.5 mg: Diutensen-R (Wallace); 0.1 mg with trichloromethiazide: 2 mg: Metatensin #2 (with tartrazine) (Merrell Dow); 0.1 mg with trichlormethiazide 4 mg: Diurese-R (American Urologicals), Metatensin #4 (Merrell Dow), Naquival (with tatazine) (Schering), Trichlormethanizide with resperpine tablets (Bolar, Moore); Trichlortensin (Rugby); 0.125 mg with chlorothiazide 250 mg: Chloroserp-250 (Quality Generics), Chloroserpine-250 (Rugby, Schein), Diupres 250.

For more Formulations/Preparations (Complete) data for RESERPINE (10 total), please visit the HSDB record page.

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.)-: ACTIVE

/SRP: Reserpine/ is synthesizable, but not commercially economically feasible. Therefore, companies extract it from the natural product./

A parenteral dosage form of /reserpine/ is no longer commerically available in the USA.

It is a crystalline alkaloid derived from Rauwolfia serpentina.