Identification

Name
Reserpine
Accession Number
DB00206  (APRD00472)
Type
Small Molecule
Groups
Approved, Investigational
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.

Structure
Thumb
Synonyms
  • (−)-reserpine
  • (3beta,16beta,17alpha,18beta,20alpha)-11,17-Dimethoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-carboxylic acid methyl ester
  • 3,4,5-trimethoxybenzoyl methyl reserpate
  • Reserpin
External IDs
ENT-50146 / NSC-237659 / NSC-59272
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ReserpineTablet0.1 mg/1OralEon Labs, Inc.1988-03-112013-07-31Us
ReserpineTablet0.25 mg/1OralPhysicians Total Care, Inc.1988-03-112002-06-30Us
ReserpineTablet0.25 mg/1OralEon Labs, Inc.1988-03-112013-07-31Us
ReserpineTablet0.1 mg/1OralPhysicians Total Care, Inc.1988-03-112002-06-30Us
Serpasil 0.25mgTablet0.25 mgOralNovartis1954-12-311999-08-04Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Novo-reserpine Tab 0.25mgTablet.25 mgOralNovopharm Limited1967-12-312005-08-10Canada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
DiupresReserpine (0.125 mg/1) + Chlorothiazide (250 mg/1)TabletOralMerck & Co., Inc.2006-03-02Not applicableUs
DiupresReserpine (0.125 mg/1) + Chlorothiazide (500 mg/1)TabletOralMerck & Co., Inc.2006-03-02Not applicableUs
Hydropres 25 TabReserpine (.125 mg) + Hydrochlorothiazide (25 mg)TabletOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1959-12-312000-06-14Canada
Hydropres 50 TabReserpine (.125 mg) + Hydrochlorothiazide (50 mg)TabletOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1959-12-311998-08-14Canada
Renese-RReserpine (25 mg/1) + Polythiazide (2 mg/1)TabletOralUNSPECIFIED2006-02-06Not applicableUs
Ser-Ap-EsReserpine (0.1 mg/1) + Hydralazine hydrochloride (25 mg/1) + Hydrochlorothiazide (15 mg/1)Tablet, coatedOralNovartis2006-04-07Not applicableUs
Ser-AP-ES TabReserpine (0.1 mg) + Hydralazine hydrochloride (25 mg) + Hydrochlorothiazide (15 mg)TabletOralNovartis1960-12-312000-08-02Canada
International/Other Brands
Apoplon / Hiserpia / Novoreserpine / Reserfia / Serpalan / Serpanray / Serpasil
Categories
UNII
8B1QWR724A
CAS number
50-55-5
Weight
Average: 608.6787
Monoisotopic: 608.273380888
Chemical Formula
C33H40N2O9
InChI Key
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
IUPAC Name
methyl (1R,15S,17R,18R,19S,20S)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyloxy)-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

Pharmacology

Indication

Foe the treatment of hypertension

Associated Conditions
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.

TargetActionsOrganism
ASynaptic vesicular amine transporter
inhibitor
Human
UChromaffin granule amine transporter
inhibitor
Human
UBaculoviral IAP repeat-containing protein 5Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

62%

Metabolism
Not Available
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineReserpine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineReserpine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Reserpine.
4-Bromo-2,5-dimethoxyamphetamineReserpine may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Reserpine is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Reserpine is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Reserpine is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Reserpine is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AbacavirReserpine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Reserpine.
Food Interactions
  • Magnesium, potassium and zinc needs increased.
  • Take with food to reduce irritation. Avoid alcohol.

References

General References
  1. Authors unspecified: 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:490882]
  2. Authors unspecified: 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:4862069]
  3. Authors unspecified: 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:2046107]
  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:12748199]
  5. Moser M: "Cost containment" in the management of hypertension. Ann Intern Med. 1987 Jul;107(1):107-9. [PubMed:3592424]
External Links
Human Metabolome Database
HMDB0014351
KEGG Drug
D00197
KEGG Compound
C06539
PubChem Compound
5770
PubChem Substance
46505863
ChemSpider
5566
BindingDB
50017712
ChEBI
28487
ChEMBL
CHEMBL772
Therapeutic Targets Database
DAP000755
PharmGKB
PA451236
Drugs.com
Drugs.com Drug Page
Wikipedia
Reserpine
ATC Codes
C02LA51 — Reserpine and diuretics, combinations with other drugsC02AA52 — Reserpine, combinationsC02LA01 — Reserpine and diureticsC02LA71 — Reserpine and diuretics, combinations with psycholepticsC02AA02 — Reserpine
MSDS
Download (73.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Not Yet RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
1Unknown StatusTreatmentAmphetamine-Related Disorders1
2CompletedTreatmentCardiovascular Disease (CVD) / Heart Diseases / High Blood Pressure (Hypertension) / Vascular Diseases1
2CompletedTreatmentCocaine-Related Disorders / Substance-Related Disorders1
2RecruitingTreatmentRefractory Hypertension1
3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension) / High Cholesterol / Type 2 Diabetes Mellitus1
3CompletedPreventionCardiovascular Disease (CVD) / Cerebrovascular Disorders / Heart Diseases / High Blood Pressure (Hypertension)1

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
  • Apotheca Inc.
  • C.O. Truxton Inc.
  • Carlisle Laboratories Inc.
  • Dispensing Solutions
  • Eon Labs
  • H and H Laboratories
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Physicians Total Care Inc.
  • Quality Research Pharmaceutical Inc.
  • United Research Laboratories Inc.
Dosage forms
FormRouteStrength
TabletOral.25 mg
TabletOral0.1 mg/1
TabletOral0.25 mg/1
Tablet, coatedOral
TabletOral
TabletOral0.25 mg
Prices
Unit descriptionCostUnit
Reserpine 0.25 mg tablet1.52USD tablet
Reserpine 0.1 mg tablet0.83USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)264.5 °CPhysProp
water solubility73 mg/L (at 30 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP3.2Not Available
pKa6.6MERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility0.0113 mg/mLALOGPS
logP4.05ALOGPS
logP3.53ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)16.29ChemAxon
pKa (Strongest Basic)7.39ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area117.78 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity161.42 m3·mol-1ChemAxon
Polarizability66.06 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9216
Blood Brain Barrier+0.9257
Caco-2 permeable+0.6549
P-glycoprotein substrateSubstrate0.7928
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IINon-inhibitor0.75
Renal organic cation transporterInhibitor0.5194
CYP450 2C9 substrateNon-substrate0.8859
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7065
CYP450 1A2 substrateInhibitor0.8965
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9384
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7062
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9439
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.1297 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7505
hERG inhibition (predictor II)Non-inhibitor0.6194
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (10.3 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-052b-0944108000-d2416a07c507dd693e2b
Mass Spectrum (Electron Ionization)MSsplash10-0002-2943000000-8f7998aa667566277f3f
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0006-0000090000-a4f3a4e74644a66e8705
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0006-0000090000-22aa398156f73127b459
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0006-0000090000-1a35ce10a9657b978845
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0006-0000090000-f1a507980fe5d4bc47a4
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0108920000-d8cec36e08efb0c1e16e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000009000-2bafaa3238dfda9f4989
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0916102000-d591ae99a68ca35e63b7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-006t-0911000000-1cb6207a1835b7efb13a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00dj-0910000000-550f1f23f96cefe74849
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-05gi-1910000000-9dd2d1b6087fe8b9d1c9
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-1910000000-7038e3a2f74fff79f220
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000009000-ea7c0832701dc10b3266
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0916103000-b1128c59f469bc4d949f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-006t-0911000000-8109e56a0558f3f60659
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00dj-0910000000-c3773763c7f72b03b234
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-05gi-1910000000-21728d59759dc657e49b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-001i-1910000000-bf727df9cb8b3d8296a0
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0108920000-29c40cb6bef71c53750f
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0000009000-0004d3aa672941e611c5
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0000009000-523f001c9c32d1385552
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0101009000-69cc395149f9a4451b3f
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0002-0915103000-a4c1fb5ec768bc8c97cb
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-006t-0912000000-cf0f8684c8b84f7e412e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0000009000-c668164b87d533a8d8f3
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0000009000-ff4084f4af36b83b2568
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0002009000-f6df1d086abaff8888d5
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-052b-0319207000-0b0edf20dde921411913
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0002-0539201000-768cf840a0a7d1abe7f6
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0003910000-4557ca8877fd85a69ba8
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0009810000-30ee17a44c90d99c4cf7
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0007920000-e0f73b5fcd3ba69e3f41
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0107920000-9a797cdf56ac618b8436
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0107920000-20d36b2dee2d9984b454
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0002-0117920000-0f76604f9bf51d86cd1f
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-01ot-0117946000-0613998d589b96bffcb8
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0002-0108944000-e6ce6049b8052a65fb14
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0002-0009832000-18eb565a7321f719807f
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0lei-6922345625-0ad422142580b61b19ef
MS/MS Spectrum - , positiveLC-MS/MSsplash10-08fs-1823119000-ee81332e154356c9dc3b
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-2923100000-57ebb3f9ade6bbbee040

Taxonomy

Description
This compound belongs to the class of organic compounds known as yohimbine alkaloids. These are alkaloids containing the pentacyclic yohimban skeleton. The Yohimbinoid alkaloids contain a carbocyclic ring E arising through C-17 to C-18 bond formation in a corynantheine precursor.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Yohimbine alkaloids
Sub Class
Not Available
Direct Parent
Yohimbine alkaloids
Alternative Parents
Corynanthean-type alkaloids / Beta carbolines / Gallic acid and derivatives / M-methoxybenzoic acids and derivatives / P-methoxybenzoic acids and derivatives / 3-alkylindoles / Benzoic acid esters / Anisoles / Methoxybenzenes / Phenoxy compounds
show 16 more
Substituents
Yohimbine / Corynanthean skeleton / Yohimbine alkaloid / Pyridoindole / Beta-carboline / Gallic acid or derivatives / P-methoxybenzoic acid or derivatives / M-methoxybenzoic acid or derivatives / Benzoate ester / 3-alkylindole
show 36 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
alkaloid ester, yohimban alkaloid (CHEBI:28487) / Indole alkaloids, Alkaloids (C06539)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Monoamine transmembrane transporter activity
Specific Function
Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles...
Gene Name
SLC18A2
Uniprot ID
Q05940
Uniprot Name
Synaptic vesicular amine transporter
Molecular Weight
55712.075 Da
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:17139284]
  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:17016423]
  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:17559790]
  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:8525459]
  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:1438304]
  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. doi: 10.1016/j.neuint.2010.02.011. Epub 2010 Feb 20. [PubMed:20176067]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serotonin transmembrane transporter activity
Specific Function
Involved in the transport of biogenic monoamines, such as serotonin, from the cytoplasm into the secretory vesicles of neuroendocrine and endocrine cells.
Gene Name
SLC18A1
Uniprot ID
P54219
Uniprot Name
Chromaffin granule amine transporter
Molecular Weight
56256.71 Da
References
  1. Ashe KM, Chiu WL, Khalifa AM, Nicolas AN, Brown BL, De Martino RR, Alexander CP, Waggener CT, Fischer-Stenger K, Stewart JK: Vesicular monoamine transporter-1 (VMAT-1) mRNA and immunoreactive proteins in mouse brain. Neuro Endocrinol Lett. 2011;32(3):253-8. [PubMed:21712771]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis. Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignmen...
Gene Name
BIRC5
Uniprot ID
O15392
Uniprot Name
Baculoviral IAP repeat-containing protein 5
Molecular Weight
16388.555 Da
References
  1. Wang Z, Guo X, Liu Z, Cui M, Song F, Liu S: Studies on alkaloids binding to GC-rich human survivin promoter DNA using positive and negative ion electrospray ionization mass spectrometry. J Mass Spectrom. 2008 Mar;43(3):327-35. [PubMed:17968851]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxygen binding
Specific Function
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  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:8632764]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
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:11297522]
  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:8632764]
  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:11716514]
  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:11961113]
  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:12134945]
  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:12636153]
  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:14985103]
  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:12235267]
  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:11602674]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
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-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
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:7990927]
Details
3. Bile salt export pump
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
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:12739759]
  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:10617675]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
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:12134946]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
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:9812985]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [PubMed:22541068]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 22:02