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Details

Stereochemistry ABSOLUTE
Molecular Formula C41H63NO14
Molecular Weight 793.9372
Optical Activity UNSPECIFIED
Defined Stereocenters 19 / 19
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PROTOVERATRINE A

SMILES

[H][C@@]12C[C@]34O[C@]5(O)[C@H](CC[C@@]3(C)[C@]5([H])[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@@]4([H])[C@]1(O)[C@@H](OC(=O)[C@H](C)CC)[C@H](O)[C@@]6([H])[C@@]2([H])CN7C[C@@H](C)CC[C@@]7([H])[C@@]6(C)O)OC(=O)[C@@](C)(O)CC

InChI

InChIKey=HYTGGNIMZXFORS-MGYKWWNKSA-N
InChI=1S/C41H63NO14/c1-10-20(4)34(46)55-33-28(45)27-23(18-42-17-19(3)12-13-25(42)38(27,9)49)24-16-39-32(40(24,33)50)30(53-22(6)44)29(52-21(5)43)31-36(39,7)15-14-26(41(31,51)56-39)54-35(47)37(8,48)11-2/h19-20,23-33,45,48-51H,10-18H2,1-9H3/t19-,20+,23-,24-,25-,26-,27+,28+,29-,30+,31-,32+,33-,36-,37-,38+,39+,40-,41+/m0/s1

HIDE SMILES / InChI

Description

Protoveratrine A, the principal alkaloid of Veratrum album, has been used in the treatment of hypertension but has largely been replaced by drugs with fewer adverse effects.

Originator

Salzberger, G.
7
Curator's Comment: Protoveratrine was first isolated by Salzberger in 1890.

Approval Year

1953
193
Targets

Targets

Primary TargetPharmacologyConditionPotency
Modulator
828
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase I
428
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
21 ng/mL
EXPERIMENT
https://link.springer.com/article/10.1365%2Fs10337-008-0936-4
12.5 μg/kg bw single, intravenous
dose: 12.5 μg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PROTOVERATRINE A plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
23.5 ng/mL
EXPERIMENT
https://link.springer.com/article/10.1365%2Fs10337-008-0936-4
0.4 mg/kg single, oral
dose: 0.4 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROTOVERATRINE A plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
44.7 ng × h/mL
EXPERIMENT
https://link.springer.com/article/10.1365%2Fs10337-008-0936-4
12.5 μg/kg bw single, intravenous
dose: 12.5 μg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PROTOVERATRINE A plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
494.9 ng × h/mL
EXPERIMENT
https://link.springer.com/article/10.1365%2Fs10337-008-0936-4
0.4 mg/kg single, oral
dose: 0.4 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROTOVERATRINE A plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21.4 h
EXPERIMENT
https://link.springer.com/article/10.1365%2Fs10337-008-0936-4
12.5 μg/kg bw single, intravenous
dose: 12.5 μg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PROTOVERATRINE A plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
21.9 h
EXPERIMENT
https://link.springer.com/article/10.1365%2Fs10337-008-0936-4
0.4 mg/kg single, oral
dose: 0.4 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROTOVERATRINE A plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
3.6 mg 1 times / day multiple, oral
Studied dose
Dose: 3.6 mg, 1 times / day
Route: oral
Route: multiple
Dose: 3.6 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/13460332
unhealthy, 40-56 years
n = 2
Health Status: unhealthy
Condition: HYPERTENSION
Age Group: 40-56 years
Sex: M
Population Size: 2
Sources:
https://pubmed.ncbi.nlm.nih.gov/13460332
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea
Vomiting
Sources:
https://pubmed.ncbi.nlm.nih.gov/13460332
1.4 mg single, oral
Highest studied dose
Dose: 1.4 mg
Route: oral
Route: single
Dose: 1.4 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/13378636
unhealthy
Health Status: unhealthy
Sources:
https://pubmed.ncbi.nlm.nih.gov/13378636
Sources:
https://pubmed.ncbi.nlm.nih.gov/13378636
2.5 ug/kg single, intravenous
Highest studied dose
Dose: 2.5 ug/kg
Route: intravenous
Route: single
Dose: 2.5 ug/kg
Sources:
https://pubmed.ncbi.nlm.nih.gov/13785790
unhealthy
n = 10
Health Status: unhealthy
Condition: hypertension
Population Size: 10
Sources:
https://pubmed.ncbi.nlm.nih.gov/13785790
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (5 patients)
Vomiting (2 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/13785790
AEs

AEs

AESignificanceDosePopulation
Nausea
3.6 mg 1 times / day multiple, oral
Studied dose
Dose: 3.6 mg, 1 times / day
Route: oral
Route: multiple
Dose: 3.6 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/13460332
unhealthy, 40-56 years
n = 2
Health Status: unhealthy
Condition: HYPERTENSION
Age Group: 40-56 years
Sex: M
Population Size: 2
Sources:
https://pubmed.ncbi.nlm.nih.gov/13460332
Vomiting
3.6 mg 1 times / day multiple, oral
Studied dose
Dose: 3.6 mg, 1 times / day
Route: oral
Route: multiple
Dose: 3.6 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/13460332
unhealthy, 40-56 years
n = 2
Health Status: unhealthy
Condition: HYPERTENSION
Age Group: 40-56 years
Sex: M
Population Size: 2
Sources:
https://pubmed.ncbi.nlm.nih.gov/13460332
Vomiting 2 patients
2.5 ug/kg single, intravenous
Highest studied dose
Dose: 2.5 ug/kg
Route: intravenous
Route: single
Dose: 2.5 ug/kg
Sources:
https://pubmed.ncbi.nlm.nih.gov/13785790
unhealthy
n = 10
Health Status: unhealthy
Condition: hypertension
Population Size: 10
Sources:
https://pubmed.ncbi.nlm.nih.gov/13785790
Nausea 5 patients
2.5 ug/kg single, intravenous
Highest studied dose
Dose: 2.5 ug/kg
Route: intravenous
Route: single
Dose: 2.5 ug/kg
Sources:
https://pubmed.ncbi.nlm.nih.gov/13785790
unhealthy
n = 10
Health Status: unhealthy
Condition: hypertension
Population Size: 10
Sources:
https://pubmed.ncbi.nlm.nih.gov/13785790
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
OATP1B1
788

OATP1B3
706
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
OATP1B1
803
 yes [Inhibition 10 uM]
OATP1B3
715
 yes [Inhibition 10 uM]
Sourcing

Sourcing

Vendor/AggregatorIDURL
ABI Chem
AC1L1RZ7
Alfa Chemistry
AP143577
https://reagents.alfa-chemistry.com/product/protoveratrine-a-cas-143-57-7-4932.html
Alfa Chemistry
143-57-7
https://www.alfa-chemistry.com/cas_143-57-7.htm
Aurora Fine Chemicals LLC
A17.912.463
http://online.aurorafinechemicals.com/info?ID=A17.912.463
BOC Sciences
143-57-7
Chemieliva Pharmaceutical Co., Ltd
PBCM0280320
Compound Cloud
8931
Parchem
57928
https://www.parchem.com/chemical-supplier-distributor/Protoveratrine-A-057928.aspx
Sigma Aldrich
P6385
Sigma Aldrich
P6385|SIGMA
Sigma-Aldrich
P6385_SIGMA
https://www.sigmaaldrich.com/catalog/product/sigma/p6385?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule
S567404
https://www.smolecule.com/products/s567404
ZINC
ZINC000085537146
http://zinc15.docking.org/substances/ZINC000085537146
abcr GmbH
AB167916
http://www.abcr.com/shop/en/AB167916
eNovation Chemicals
D512302
http://www.enovationchem.com/productDetails.asp?productID=D512302
PubMed

PubMed

TitleDatePubMed
The use of protoveratrine in the treatment of hypertensive vascular disease.
1953 Oct
Protoveratrine A in treatment of hypertension.
1957 Sep 14
Patents

Patents

US20030068365
9
US2929812
5
US3456049
5
US3634583
5

Sample Use Guides

In Vivo Use Guide
Out-patient Treatment of hypertension with Protoveratrine A: The duration of treatment has been from one month to as long as two years (mean nine months). The total treatment months were 155. The dosage employed varied from 0.5 to 3.6 mg daily. The drug was taken three times daily after meals and an additional dose often on retiring.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: Protoveratrine A (10(-4) M), on the other hand, elevated the efflux of glutamate, GABA and possibly aspartate when these amino acids were synthesised from glucose, but not when acetate was the labelled precursor. https://www.ncbi.nlm.nih.gov/pubmed/913529
Protoveratrine A increased the release of gamma-amino[3H]butyrate from small slices of rat cerebral cortex. This effect increased with increasing protoveratrine concentration, reaching a maximum at 100 uM. 2. Removal of Ca2+ from the superfusing medium did not change the increase in release due to 10 uM-protoveratrine.
Name Type Language
PROTOVERATRINE A
MI   WHO-DD  
Common Name English
CEVANE-3,4,6,7,14,15,16,20-OCTOL, 4,9-EPOXY-, 6,7-DIACETATE 3-(2-HYDROXY-2-METHYLBUTANOATE) 15-(2-METHYLBUTANOATE), (3.BETA.(S),4.ALPHA.,6.ALPHA.,7.ALPHA.,15.ALPHA.(R),16.BETA.)-
Systematic Name English
PROTOVERATRINE A [MI]
Common Name English
CEVANE-3,4,6,7,14,15,16,20-OCTOL, 4,9-EPOXY-, 6,7-DIACETATE 3-((2S)-2-HYDROXY-2-METHYLBUTANOATE) 15-((2R)-2-METHYLBUTANOATE), (3.BETA.,4.ALPHA.,6.ALPHA.,7.ALPHA.,15.ALPHA.,16.BETA.)-
Systematic Name English
PROTALBA
Brand Name English
(3.BETA.(S),4.ALPHA.,6.ALPHA.,7.ALPHA.,15.ALPHA.(R),16.BETA.)-4,9-EPOXYCEVANE-3,4,6,7,14,15,16,20-OCTOL 6,7-DIACETATE 3-(2-HYDROXY-2-METHYLBUTANOATE) 15-(2-METHYLBUTANOATE)
Common Name English
NSC-7526
Code English
Protoveratrine a [WHO-DD]
Common Name English
PROTOVERATRIN
Common Name English
PROTOVERATRINE
Common Name English
NSC-23865
Code English
PROTOVERINE 3-((+)-(2S)-2-HYDROXY-2-METHYLBUTYRATE) 6,7-DIACETATE 15-((-)-(2R)-2-METHYLBUTYRATE)
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C221
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
Code System Code Type Description
FDA UNII
XP343X1HJU
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
PRIMARY
NSC
7526
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
PRIMARY
NCI_THESAURUS
C81361
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
PRIMARY
ECHA (EC/EINECS)
205-602-9
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
PRIMARY
NSC
23865
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
PRIMARY
ChEMBL
CHEMBL2105769
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
PRIMARY
CAS
143-57-7
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
PRIMARY
EVMPD
SUB36172
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
PRIMARY
MERCK INDEX
m9278
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID301009391
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
PRIMARY
SMS_ID
100000128725
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
PRIMARY
PUBCHEM
8931
Created by admin on Fri Dec 15 15:39:22 GMT 2023 , Edited by admin on Fri Dec 15 15:39:22 GMT 2023
PRIMARY
SALT/SOLVATE (PARENT)
Structure of PROTOVERATRINE A MALEATE
NIH
NCATS
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