Identification

Name
Deserpidine
Accession Number
DB01089  (APRD00906)
Type
Small Molecule
Groups
Approved
Description

Deserpidine is an ester alkaloid drug isolated from Rauwolfia canescens (family Apocynaceae) with antipsychotic and antihypertensive properties that has been used for the control of high blood pressure and for the relief of psychotic behavior.

Structure
Thumb
Synonyms
  • (3beta,16beta,17alpha,18beta,20alpha)-17-Methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-carboxylic acid methyl ester
  • 11-demethoxyreserpine
  • 11-desmethoxyreserpine
  • Canescine
  • Deserpidina
  • Deserpidine
  • Deserpidinum
  • Raunormine
  • Recanescine
Product Ingredients
IngredientUNIICASInChI Key
Deserpidine hydrochloride6LPC48045D6033-69-8YCNOGQOHKRDAHJ-UZXCFUCJSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
EnduronylDeserpidine (0.25 mg/1) + Methyclothiazide (5 mg/1)TabletOralAbbvie1961-08-012002-04-30Us
EnduronylDeserpidine (0.25 mg/1) + Methyclothiazide (5 mg/1)TabletOralPhysicians Total Care, Inc.1961-08-012006-12-31Us
Enduronyl ForteDeserpidine (0.5 mg/1) + Methyclothiazide (5 mg/1)TabletOralAbbvie1961-08-012001-04-30Us
International/Other Brands
Harmonyl (Abbott)
Categories
UNII
9016E3VB47
CAS number
131-01-1
Weight
Average: 578.6527
Monoisotopic: 578.262816202
Chemical Formula
C32H38N2O8
InChI Key
CVBMAZKKCSYWQR-WCGOZPBSSA-N
InChI
InChI=1S/C32H38N2O8/c1-37-24-12-17(13-25(38-2)29(24)39-3)31(35)42-26-14-18-16-34-11-10-20-19-8-6-7-9-22(19)33-28(20)23(34)15-21(18)27(30(26)40-4)32(36)41-5/h6-9,12-13,18,21,23,26-27,30,33H,10-11,14-16H2,1-5H3/t18-,21+,23-,26-,27+,30+/m1/s1
IUPAC Name
methyl (1R,15S,17R,18R,19S,20S)-18-methoxy-17-(3,4,5-trimethoxybenzoyloxy)-3,13-diazapentacyclo[11.8.0.0²,¹⁰.0⁴,⁹.0¹⁵,²⁰]henicosa-2(10),4,6,8-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=CC=CC=C31)C2

Pharmacology

Indication

For the treatment of hypertension.

Pharmacodynamics

Deserpidine, an alkaloid of Rauwolfia canescens, is used as an antihypertensive. Rauwolfia alkaloids work by controlling nerve impulses along certain nerve pathways. As a result, they act on the heart and blood vessels to lower blood pressure.

Mechanism of action

Deserpidine'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
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose include dizziness or drowsiness (severe), flushing of skin, pinpoint pupils of eyes and slowed pulse.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcebutololDeserpidine may increase the hypotensive activities of Acebutolol.
AceclofenacThe therapeutic efficacy of Deserpidine can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Deserpidine can be decreased when used in combination with Acemetacin.
Acetylsalicylic acidThe therapeutic efficacy of Deserpidine can be decreased when used in combination with Acetylsalicylic acid.
AlclofenacThe therapeutic efficacy of Deserpidine can be decreased when used in combination with Alclofenac.
AlfuzosinAlfuzosin may increase the hypotensive activities of Deserpidine.
AliskirenDeserpidine may increase the hypotensive activities of Aliskiren.
AlminoprofenThe therapeutic efficacy of Deserpidine can be decreased when used in combination with Alminoprofen.
AlprenololAlprenolol may increase the hypotensive activities of Deserpidine.
AmbrisentanDeserpidine may increase the hypotensive activities of Ambrisentan.
Food Interactions
Not Available

References

Synthesis Reference

Gabriele Fontana, Ezio Bombardelli, Cristian Samori, Eleonora Baldelli, Andrea Guerrini, Arturo Battaglia, Bruno Danieli, "Process for the Semisynthesis of Deserpidine." U.S. Patent US20080242864, issued October 02, 2008.

US20080242864
General References
Not Available
External Links
Human Metabolome Database
HMDB0015221
KEGG Compound
C06541
PubChem Compound
8550
PubChem Substance
46505311
ChemSpider
8232
ChEBI
27478
ChEMBL
CHEMBL1200515
Therapeutic Targets Database
DAP000909
PharmGKB
PA164742966
Wikipedia
Deserpidine
ATC Codes
C02AA05 — DeserpidineC02LA03 — Deserpidine and diuretics

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)228-232Ulshafer, P.R.; US. Patent 2,982,769; May 2, 1961; assigned to Ciba Pharmaceutical.
logP3.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0111 mg/mLALOGPS
logP4.25ALOGPS
logP3.69ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)16.37ChemAxon
pKa (Strongest Basic)7.57ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area108.55 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity154.96 m3·mol-1ChemAxon
Polarizability62.59 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9353
Blood Brain Barrier+0.9496
Caco-2 permeable+0.6582
P-glycoprotein substrateSubstrate0.8178
P-glycoprotein inhibitor IInhibitor0.8302
P-glycoprotein inhibitor IINon-inhibitor0.8096
Renal organic cation transporterInhibitor0.5326
CYP450 2C9 substrateNon-substrate0.894
CYP450 2D6 substrateNon-substrate0.8761
CYP450 3A4 substrateSubstrate0.7198
CYP450 1A2 substrateInhibitor0.8392
CYP450 2C9 inhibitorNon-inhibitor0.8701
CYP450 2D6 inhibitorNon-inhibitor0.9064
CYP450 2C19 inhibitorNon-inhibitor0.8954
CYP450 3A4 inhibitorNon-inhibitor0.8353
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7081
Ames testNon AMES toxic0.9234
CarcinogenicityNon-carcinogens0.9484
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.0921 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7952
hERG inhibition (predictor II)Non-inhibitor0.6277
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-014i-7967010000-b3758c647fba3c682e47
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

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
organic heteropentacyclic compound, methyl ester, benzoate ester, alkaloid ester, yohimban alkaloid (CHEBI:27478) / Indole alkaloids (C06541)

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. 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]
  2. 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]
  3. 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]
  4. 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]
  5. Fulton SC, Healy MD: Comparison of the effectiveness of deserpidine, reserpine, and alpha-methyltyrosine on brain biogenic amines. Fed Proc. 1976 Dec;35(14):2558-62. [PubMed:11134]
  6. Loeffler LJ, Schran HF: Antibody specificity studies for reserpine, its metabolites, and synthetic reserpine congeners: radioimmunoassay. J Pharm Sci. 1979 Nov;68(11):1433-5. [PubMed:574544]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 09:06