PROTOVERATRINE B TANNATE

US Previously Marketed

First approved in 1953

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C76H52O46.C41H63NO15
Molecular Weight	2511.1351
Optical Activity	UNSPECIFIED
Defined Stereocenters	25 / 25
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

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)[C@@H](C)O.OC8=CC(=CC(O)=C8O)C(=O)OC9=CC(=CC(O)=C9O)C(=O)OC[C@H]%10O[C@@H](OC(=O)C%11=CC(O)=C(O)C(OC(=O)C%12=CC(O)=C(O)C(O)=C%12)=C%11)[C@H](OC(=O)C%13=CC(O)=C(O)C(OC(=O)C%14=CC(O)=C(O)C(O)=C%14)=C%13)[C@@H](OC(=O)C%15=CC(O)=C(O)C(OC(=O)C%16=CC(O)=C(O)C(O)=C%16)=C%15)[C@@H]%10OC(=O)C%17=CC(O)=C(O)C(OC(=O)C%18=CC(O)=C(O)C(O)=C%18)=C%17

InChI

InChIKey=SOQCMFOQBKVHBY-AUUQKRJOSA-N

InChI=1S/C76H52O46.C41H63NO15/c77-32-1-22(2-33(78)53(32)92)67(103)113-47-16-27(11-42(87)58(47)97)66(102)112-21-52-63(119-72(108)28-12-43(88)59(98)48(17-28)114-68(104)23-3-34(79)54(93)35(80)4-23)64(120-73(109)29-13-44(89)60(99)49(18-29)115-69(105)24-5-36(81)55(94)37(82)6-24)65(121-74(110)30-14-45(90)61(100)50(19-30)116-70(106)25-7-38(83)56(95)39(84)8-25)76(118-52)122-75(111)31-15-46(91)62(101)51(20-31)117-71(107)26-9-40(85)57(96)41(86)10-26;1-10-19(3)34(47)56-33-28(46)27-23(17-42-16-18(2)11-12-25(42)38(27,9)50)24-15-39-32(40(24,33)51)30(54-22(6)45)29(53-21(5)44)31-36(39,7)14-13-26(41(31,52)57-39)55-35(48)37(8,49)20(4)43/h1-20,52,63-65,76-101H,21H2;18-20,23-33,43,46,49-52H,10-17H2,1-9H3/t52-,63-,64+,65-,76+;18-,19+,20+,23-,24-,25-,26-,27+,28+,29-,30+,31-,32+,33-,36-,37+,38+,39+,40-,41+/m10/s1

HIDE SMILES / InChI

Molecular Formula	C41H63NO15
Molecular Weight	809.9366
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	20 / 20
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C76H52O46
Molecular Weight	1701.1985
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/13378636 | https://medical-dictionary.thefreedictionary.com/protoveratrine+A+and+B | https://www.ncbi.nlm.nih.gov/pubmed/14065377 | https://www.ncbi.nlm.nih.gov/pubmed/13516706 | https://www.ncbi.nlm.nih.gov/pubmed/25379034

Protoveratrine B is one of two alkaloids isolated from the plant Veratrum albumen. The main effect of both alkaloids is vasodilation in all vascular beds thereby reducing blood pressure. In the 1950's it was recognized that Protoveratrine B is the preferred compound which can be administered at significantly higher doses before the patient begins to vomit.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
voltage-gated sodium channel activity 12 Target ID: GO:0005248 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25379034	Opener 34

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: https://www.ncbi.nlm.nih.gov/pubmed/13378636 https://www.ncbi.nlm.nih.gov/pubmed/13516706 https://www.ncbi.nlm.nih.gov/pubmed/25379034	Primary		Not Provided 504	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
402 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19021933/	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered:		PROTOVERATRINE B plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
17 mg multiple, oral Highest studied dose Dose: 17 mg Route: oral Route: multiple Dose: 17 mg Sources: https://pubmed.ncbi.nlm.nih.gov/13378636	unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13378636	Other AEs: Nausea, Vomiting... Other AEs: Nausea Vomiting Lightheadedness Throat burning sensation of (mild) Sources: https://pubmed.ncbi.nlm.nih.gov/13378636
7.5 mg single, oral Highest studied dose Dose: 7.5 mg Route: oral Route: single Dose: 7.5 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
4.3 ug/kg single, intravenous Highest studied dose Dose: 4.3 ug/kg Route: intravenous Route: single Dose: 4.3 ug/kg Sources: https://pubmed.ncbi.nlm.nih.gov/13785790	unhealthy n = 13 Health Status: unhealthy Condition: hypertension Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/13785790	Other AEs: Nausea... Other AEs: Nausea (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/13785790

AEs

AE	Significance	Dose	Population
Lightheadedness		17 mg multiple, oral Highest studied dose Dose: 17 mg Route: oral Route: multiple Dose: 17 mg Sources: https://pubmed.ncbi.nlm.nih.gov/13378636	unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13378636
Nausea		17 mg multiple, oral Highest studied dose Dose: 17 mg Route: oral Route: multiple Dose: 17 mg Sources: https://pubmed.ncbi.nlm.nih.gov/13378636	unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13378636
Vomiting		17 mg multiple, oral Highest studied dose Dose: 17 mg Route: oral Route: multiple Dose: 17 mg Sources: https://pubmed.ncbi.nlm.nih.gov/13378636	unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13378636
Throat burning sensation of	mild	17 mg multiple, oral Highest studied dose Dose: 17 mg Route: oral Route: multiple Dose: 17 mg Sources: https://pubmed.ncbi.nlm.nih.gov/13378636	unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13378636
Nausea	2 patients	4.3 ug/kg single, intravenous Highest studied dose Dose: 4.3 ug/kg Route: intravenous Route: single Dose: 4.3 ug/kg Sources: https://pubmed.ncbi.nlm.nih.gov/13785790	unhealthy n = 13 Health Status: unhealthy Condition: hypertension Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/13785790

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B1 788 OATP1B3 706

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OATP1B1 803	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxNjUzOTgifX0%3D, https://pubmed.ncbi.nlm.nih.gov/23571415/	yes [Inhibition 10 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxNjUzOTgifX0%3D, https://pubmed.ncbi.nlm.nih.gov/23571415/	yes

Sourcing

Vendor/Aggregator	ID	URL
AAA Chemistry	AR-1A5051
ABI Chem	AC1L1JC9
ABI Chem	AC1L5BDZ
ABI Chem	AC1L9DSH
Alfa Chemistry	124-97-0
Ambinter	Amb22729630	http://www.ambinter.com/reference/22729630
BOC Sciences	124-97-0
Chemieliva Pharmaceutical Co., Ltd	PBCM1125104
Japan Chemical Substance Dictionary (Nikkaji)	J9.705E	http://jglobal.jst.go.jp/en/redirect?Nikkaji_No=J9.705E
Kingston Chemistry	KST-1A1482
MetabolomicsWorkbench	69573	http://www.metabolomicsworkbench.org/data/StructureData.php?RegNo=69573
NCATS	NCGC00178306-01
NINDS Approved Drug Screening Program	1500938
THE BioTek	bt-363874	https://www.thebiotek.com/product/others/bt-363874
THE BioTek	bt-367569	https://www.thebiotek.com/product/others/bt-367569
THE BioTek	bt-371034	https://www.thebiotek.com/product/others/bt-371034
THE BioTek	bt-395131	https://www.thebiotek.com/product/others/bt-395131
ZINC	ZINC000254091663	http://zinc15.docking.org/substances/ZINC000254091663
eMolecules	43448647

PubMed

Title	Date	PubMed
A comparison between protoveratrine A and protoveratrine B orally in arterial hypertension; a therapeutically important difference in activity.	1956 Dec 20	13378636
[Protoveratrine A-B in medical therapy of hypertensive disease].	1957 Dec 22	13516706
INHIBITIONS BY OUABAIN AND PROTOVERATRINE ON ACTIVE TRANSPORT OF L-DOPA INTO BRAIN SLICES.	1963 Apr	14065377
Medicinal history of North American Veratrum.	2014 Sep	25379034

Patents

Sample Use Guides

In Vivo Use Guide

Protoveratrine B was administered to hypertensive patients as an oral tablet. Doses began at 0.3 to 0.5 mg single daily dose and raised incrementally until a marked fall in blood pressure was observed or the development on vomiting prohibited further increase.

Route of Administration: Oral

In Vitro Use Guide

Brain cortex slices of adult guinea pig were incubated for 30 min with 0.1 mM L-dopa. Brain slices were then pretreated with 5 uM protoveratrine (10 uM to 10 mM) for 20 min at 27 deg-C. Slices then incubated with glucose and L-dopa at 37 deg-C. The inclusion of Protoveratrine caused a decrease in the accumulation of L-dopa compared to control.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:06:16 GMT 2023` Edited by `admin` on `Sat Dec 16 01:06:16 GMT 2023`
Record UNII	H94DDE2EDR
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PROTOVERATRINE B TANNATE

Common Name

English

CEVANE-3,4,6,7,14,15,16,20-OCTOL, 4,9-EPOXY-, 6,7-DIACETATE 3-((2R,3R)-2,3-DIHYDROXY-2-METHYLBUTANOATE) 15-((2R)-2-METHYLBUTANOATE), (3.BETA.,4.ALPHA.,6.ALPHA.,7.ALPHA.,15.ALPHA.,16.BETA.)-, TANNATE

Common Name

English

Code System Code Type Description

PUBCHEM

165411853

Created by admin on Sat Dec 16 01:06:16 GMT 2023 , Edited by admin on Sat Dec 16 01:06:16 GMT 2023

PRIMARY

FDA UNII

H94DDE2EDR