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Identification
Name Reserpine
Accession Number DB00206 (APRD00472)
Type small molecule
Groups approved
Description

An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Cam-Ap-Es
  • Demi-Regroton
  • Diupres-250
  • Diupres-500
  • Diutensen-R
  • Dralserp
  • Hiserpia
  • Hydrap-ES
  • Hydromox R
  • Hydroserpine Plus (R-H-H)
  • Metatensin #2
  • Metatensin #4
  • Naquival
  • Novoreserpine
  • Rau-Sed
  • Regroton
  • Renese-R
  • Reserfia
  • Salutensin
  • Salutensin-Demi
  • Sandril
  • Ser-A-Gen
  • Serpalan
  • Serpanray
  • Serpasil
  • Serpasil-Apresoline
  • Serpasil-Esidrix #1
  • Serpasil-Esidrix #2
  • Serpate
  • Serpivite
  • Unipres
Brand name mixtures
  • Hydropres 25 Tab (Hydrochlorothiazide + Reserpine)
  • Hydropres 50 Tab (Hydrochlorothiazide + Reserpine)
  • SER-AP-ES Tab (Hydralazine Hydrochloride + Hydrochlorothiazide + Reserpine)
Categories
  • Antihypertensive Agents
  • Adrenergic Uptake Inhibitors
  • Antipsychotics
  • Peripheral Adrenergic Inhibitors
  • Antipsychotic Agents
CAS number 50-55-5
Weight Average: 608.6787
Monoisotopic: 608.273380888
Chemical Formula C33H40N2O9
InChI Key InChIKey=QEVHRUUCFGRFIF-MDEJGZGSSA-N
InChI
InChI=1S/C33H40N2O9/c1-38-19-7-8-20-21-9-10-35-16-18-13-27(44-32(36)17-11-25(39-2)30(41-4)26(12-17)40-3)31(42-5)28(33(37)43-6)22(18)15-24(35)29(21)34-23(20)14-19/h7-8,11-12,14,18,22,24,27-28,31,34H,9-10,13,15-16H2,1-6H3/t18-,22+,24-,27-,28+,31+/m1/s1
Plain Text
IUPAC Name
methyl (1R,15S,17R,18R,19S,20S)-6,18-dimethoxy-17-[(3,4,5-trimethoxyphenyl)carbonyloxy]-3,13-diazapentacyclo[11.8.0.0^{2,10}.0^{4,9}.0^{15,20}]henicosa-2(10),4(9),5,7-tetraene-19-carboxylate
SMILES
[H][C@]12C[C@@H](OC(=O)C3=CC(OC)=C(OC)C(OC)=C3)[C@H](OC)[C@@H](C(=O)OC)[C@@]1([H])C[C@@]1([H])N(CCC3=C1NC1=C3C=CC(OC)=C1)C2
Plain Text
Mass Spec show (10.3 KB)
Taxonomy
Kingdom Organic
Classes
  • Alkaloids and Alkaloid Derivatives
Substructures
  • Carboxylic Acids and Derivatives
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Indoles and Indole Derivatives
  • Benzoates
  • Phenols and Derivatives
  • Pyrroles
  • Alkaloids and Alkaloid Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Catechols
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Tryptamines and Derivatives
  • Imines
  • Benzoyl Derivatives
  • (Iso)quinolines and Derivatives
  • Phenyl Esters
  • Gallic Acid and Derivatives
  • Piperidines
Pharmacology
Indication Foe the treatment of hypertension
Pharmacodynamics 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.
Mechanism of action 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding 62%
Metabolism
Route of elimination Reserpine is extensively metabolized to inactive compounds. It is slowly excreted via the urine and feces.
Half life Not Available
Clearance Not Available
Toxicity Possible human carcinogen. May cause reproductive harm. ORL-RAT LD50 420 mg/kg; IPR-RAT LD50 44 mg/kg; IVN-RAT LD50 15 mg/kg; ORL-MUS LD50 200 mg/kg; SCU-MUS LD50 52 mg/kg; IPR-RBT LD50 7 mg/kg
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
  • Eli lilly and co
  • Bowman pharmaceuticals inc
  • Bristol myers squibb co
  • Barr laboratories inc
  • Bell pharmacal corp
  • Cm bundy co
  • Elkins sinn div ah robins co inc
  • Everylife
  • Halsey drug co inc
  • Impax laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Marshall pharmacal corp
  • Mk laboratories inc
  • Mylan pharmaceuticals inc
  • Pharmavite pharmaceuticals
  • Purepac pharmaceutical co
  • Private formulations inc
  • Rexall drug co
  • Roxane laboratories inc
  • Sandoz inc
  • Solvay pharmaceuticals
  • Tablicaps inc
  • Teva pharmaceuticals usa inc
  • Valeant pharmaceuticals international
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • Whiteworth towne paulsen inc
  • Lannett co inc
  • Panray corp sub ormont drug and chemical co inc
  • Vale chemical co inc
  • Vitarine pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Reserpine 0.25 mg tablet 1.52 USD tablet
Reserpine 0.1 mg tablet 0.83 USD tablet
Patents Not Available
Properties
State solid
Melting point 264.5 oC
Experimental Properties
Property Value Source
water solubility 73 mg/L PhysProp
logP 3.2 PhysProp
pKa 6.6 Various sources
Predicted Properties
Property Value Source
water solubility 1.13e-02 g/l ALOGPS
logP 4.05 ALOGPS
logP 3.53 ChemAxon Molconvert
logS -4.73 ALOGPS
pKa 16.54 ChemAxon Molconvert
hydrogen acceptor count 8 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 117.78 ChemAxon Molconvert
rotatable bond count 10 ChemAxon Molconvert
refractivity 161.42 ChemAxon Molconvert
polarizability 66.05 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. : Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA. 1979 Dec 7;242(23):2562-71. Pubmed
  2. : Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA. 1967 Dec 11;202(11):1028-34. Pubmed
  3. : Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA. 1991 Jun 26;265(24):3255-64. Pubmed
  4. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560-72. Epub 2003 May 14. Pubmed
  5. Moser M: “Cost containment” in the management of hypertension. Ann Intern Med. 1987 Jul;107(1):107-9. Pubmed
External Links
Resource Link
KEGG Drug D00197 Link_out
KEGG Compound C06539 Link_out
PubChem Compound 5770 Link_out
PubChem Substance 46505863 Link_out
ChemSpider 5566 Link_out
ChEBI 28487 Link_out
ChEMBL 28487 Link_out
Therapeutic Targets Database DAP000755 Link_out
PharmGKB PA451236 Link_out
Drug Product Database 21784 Link_out
Drugs.com http://www.drugs.com/cdi/reserpine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Reserpine Link_out
ATC Codes
  • C02AA02
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (73.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Magnesium, potassium and zinc needs increased.
  • Take with food to reduce irritation. Avoid alcohol.
Targets

1. Synaptic vesicular amine transporter

Pharmacological action: yes
Actions: inhibitor

Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis

Organism class: human
UniProt ID: Q05940 Link_out
Gene: SLC18A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Sievert MK, Hajipour AR, Ruoho AE: Specific derivatization of the vesicle monoamine transporter with novel carrier-free radioiodinated reserpine and tetrabenazine photoaffinity labels. Anal Biochem. 2007 Aug 1;367(1):68-78. Epub 2007 May 3. Pubmed
  4. Naudon L, Leroux-Nicollet I, Raisman-Vozari R, Botton D, Costentin J: Time-course of modifications elicited by reserpine on the density and mRNA synthesis of the vesicular monoamine transporter, and on the density of the membrane dopamine uptake complex. Synapse. 1995 Sep;21(1):29-36. Pubmed
  5. Erickson JD, Eiden LE, Hoffman BJ: Expression cloning of a reserpine-sensitive vesicular monoamine transporter. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10993-7. Pubmed
  6. Mandela P, Chandley M, Xu YY, Zhu MY, Ordway GA: Reserpine-induced reduction in norepinephrine transporter function requires catecholamine storage vesicles. Neurochem Int. 2010 May-Jun;56(6-7):760-7. Epub 2010 Feb 20. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Cytochrome P450 3A5

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: substrate, inhibitor, inducer

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Geick A, Eichelbaum M, Burk O: Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem. 2001 May 4;276(18):14581-7. Epub 2001 Jan 31. Pubmed
  2. Schuetz EG, Beck WT, Schuetz JD: Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol. 1996 Feb;49(2):311-8. Pubmed
  3. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
  4. Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA: Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol. 2002 May;61(5):964-73. Pubmed
  5. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):765-72. Pubmed
  6. Horie K, Tang F, Borchardt RT: Isolation and characterization of Caco-2 subclones expressing high levels of multidrug resistance protein efflux transporter. Pharm Res. 2003 Feb;20(2):161-8. Pubmed
  7. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. Pubmed
  8. Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. Pubmed
  9. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. Pubmed

2. Solute carrier family 22 member 1

Actions: inhibitor

Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)- N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin- dependent kinase II and LCK tyrosine kinase

UniProt ID: O15245 Link_out
Gene: SLC22A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Grundemann D, Gorboulev V, Gambaryan S, Veyhl M, Koepsell H: Drug excretion mediated by a new prototype of polyspecific transporter. Nature. 1994 Dec 8;372(6506):549-52. Pubmed

3. Bile salt export pump

Actions: inhibitor

Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes

UniProt ID: O95342 Link_out
Gene: ABCB11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. Pubmed
  2. Lecureur V, Sun D, Hargrove P, Schuetz EG, Kim RB, Lan LB, Schuetz JD: Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol Pharmacol. 2000 Jan;57(1):24-35. Pubmed

4. Canalicular multispecific organic anion transporter 1

Actions: inhibitor

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MRP2 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):773-9. Pubmed

5. Solute carrier family 22 member 2

Actions: substrate

Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity

UniProt ID: O15244 Link_out
Gene: SLC22A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Grundemann D, Koster S, Kiefer N, Breidert T, Engelhardt M, Spitzenberger F, Obermuller N, Schomig E: Transport of monoamine transmitters by the organic cation transporter type 2, OCT2. J Biol Chem. 1998 Nov 20;273(47):30915-20. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:02

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.