TETRAHYDROPALMATINE HYDROCHLORIDE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H25NO4.ClH
Molecular Weight	391.888
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of TETRAHYDROPALMATINE HYDROCHLORIDE

Structure Search

SMILES

Cl.[H][C@@]12CC3=C(CN1CCC4=CC(OC)=C(OC)C=C24)C(OC)=C(OC)C=C3

InChI

InChIKey=MGSZZQQRTPWMEI-LMOVPXPDSA-N

InChI=1S/C21H25NO4.ClH/c1-23-18-6-5-13-9-17-15-11-20(25-3)19(24-2)10-14(15)7-8-22(17)12-16(13)21(18)26-4;/h5-6,10-11,17H,7-9,12H2,1-4H3;1H/t17-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C21H25NO4
Molecular Weight	355.4275
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17361394 | https://www.ncbi.nlm.nih.gov/pubmed/22300097 | https://www.ncbi.nlm.nih.gov/pubmed/27363313 | Zhang, X. (2017) The Effects of L-Tetrahydropalmatine and Rhynchophylline, Alkaloids Derived from Herbal Medicines, on Cellular and Molecular Neurotoxicity of Cocaine in Pc12 Cells, page 21, retrieved from: https://books.google.ru/books?id=KetSAQAACAAJ

Tetrahydropalmatine is a tetrahydroprotoberberine isoquinoline alkaloid that is a primary active constituent of herbal preparations containing plant species of the genera Stephania and Corydalis. The levo isomer of THP (L-THP) appears to contribute to many of the therapeutic effects of these preparations. The pharmacological profile of L-THP, which includes antagonism of dopamine D1 and D2 receptors and actions at dopamine D3, suggests that it may have utility for treating addiction. Clinical trials where L-THP was used for the treatment of cocaine and heroin addiction have promising results. The clinical trial is planned for the treatment of schizophrenia. L-Tetrahydropalmatine is recorded in the Chinese pharmacopoeia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Apoptosis 155 Target ID: WP254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28721806	Activator 1430
Dopamine D1 receptor 101 Target ID: CHEMBL2056 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17361394 \| https://www.ncbi.nlm.nih.gov/pubmed/22300097	Antagonist 2778	124.0 nM [Ki]
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17361394 \| https://www.ncbi.nlm.nih.gov/pubmed/22300097	Antagonist 2778	388.0 nM [Ki]
Dopamine D3 receptor 91 Target ID: CHEMBL3138 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17361394 \| https://www.ncbi.nlm.nih.gov/pubmed/22300097	Binding Agent 1064	1.4 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 298 Sources: https://clinicaltrials.gov/ct2/show/NCT02118610	Primary	Phase II 1132	Unknown Approved Use Unknown
Cocaine use disorder 5 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22300097 https://www.ncbi.nlm.nih.gov/pubmed/27363313	Primary	Phase II 1132	Unknown Approved Use Unknown
Heroin dependence 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22300097 https://www.ncbi.nlm.nih.gov/pubmed/18565275	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
42.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27363313	30 mg 2 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TETRAHYDROPALMATINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
396.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27363313	30 mg 2 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TETRAHYDROPALMATINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
13.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27363313	30 mg 2 times / day multiple, oral dose: 30 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TETRAHYDROPALMATINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
30 mg 2 times / day multiple, oral Studied dose Dose: 30 mg, 2 times / day Route: oral Route: multiple Dose: 30 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27363313 Page: p.7, 8	healthy, ADULT n = 11 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/27363313 Page: p.7, 8	Sources: https://pubmed.ncbi.nlm.nih.gov/27363313 Page: p.7, 8

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP1A2 1524 CYP2C19 1478 MATE1 306 MRP1 106 CYP3A4/5 278 CYP2A6 707 CYP2E1 882 OCT2 647 BCRP 699 P-gp 1461	CYP1A2 1054 CYP3A4/5 85 P-gp 1537

Drug as perpetrator

Target	Modality	Activity
MATE1 308	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32389634/	moderate [IC50 20.9 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/	no
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP3A4/5 335	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
MRP1 172	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/	no
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/	weak [IC50 48.6 uM]
OCT2 648	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/32389634/	yes [IC50 2.65 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23001793/	yes [Ki 6.42 uM]

Drug as victim

Target	Modality	Activity
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006929	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23001793/	yes
CYP3A4/5 85	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23001793/	yes

PubMed

Title	Date	PubMed
Evaluation of natural products as inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.	1991 Jan-Feb	1710653
DL-tetrahydropalmatine-produced hypotension and bradycardia in rats through the inhibition of central nervous dopaminergic mechanisms.	1995 Oct	8577817
Formation of protoberberine-type alkaloids by the tubers of somatic embryo-derived plants of Corydalis yanhusuo.	2001 Dec	11745021
Influence of light and heat on the stability of rotundine sulfate injection.	2001 Oct	11745708
Effects of L-tetrahydropalmatine on the expressions of bcl-2 and bax in rat after acute global cerebral ischemia and reperfusion.	2004	15641688
Chiral liquid chromatography resolution and stereoselective pharmacokinetic study of tetrahydropalmatine enantiomers in dogs.	2005 Nov 5	16165405
Enantioseparation of tetrahydropalmatine and Tröger's base by molecularly imprinted monolith in capillary electrochromatography.	2007 Feb 23	16978700
Levo-tetrahydropalmatine attenuates cocaine self-administration and cocaine-induced reinstatement in rats.	2007 Jul	17361394
[Difference absorption of l-tetrahydropalmatine and dl-tetrahydropalmatine in intestine of rats].	2007 May	17703779
Medication of l-tetrahydropalmatine significantly ameliorates opiate craving and increases the abstinence rate in heroin users: a pilot study.	2008 Jul	18565275
[Interaction between four herb compounds and a western drug by CYP3A4 enzyme metabolism in vitro].	2009 Jul	19873787
[Comparison of microwave-assisted and conventional extraction of Corydalis yanhusuo].	2009 Jul	19873742
[Study on the influence on Rhizoma Corydalis by different harvest time and processing methods].	2009 Jul	19873726
[Bio-activity evaluation of Qinlian Siwu decoction on inhibiting mice uterine contraction in vitro and its components analysis].	2010 Dec	21438408
Screening of antinociceptive components in Corydalis yanhusuo W.T. Wang by comprehensive two-dimensional liquid chromatography/tandem mass spectrometry.	2010 Mar	20101504

Patents

Sample Use Guides

In Vivo Use Guide

30 mg twice daily (7 total doses)

Route of Administration: Oral

In Vitro Use Guide

Co-incubation with L-THP (0.01-1ug/ml) did not produce significant effects on 500 uM cocaine-inhibited neurite growth in PC12 cells either at low or high doses.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 08:28:28 GMT 2023` Edited by `admin` on `Sat Dec 16 08:28:28 GMT 2023`
Record UNII	RH72T8K75E
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TETRAHYDROPALMATINE HYDROCHLORIDE

Common Name

English

13A.ALPHA.-BERBINE, 2,3,9,10-TETRAMETHOXY-, HYDROCHLORIDE

Common Name

English

GINDARINE HYDROCHLORIDE

Common Name

English

Tetrahydropalmatine hydrochloride [WHO-DD]

Common Name

English

6H-DIBENZO(A,G)QUINOLIZINE, 5,8,13,13A-TETRAHYDRO-2,3,9,10-TETRAMETHOXY-, HYDROCHLORIDE (1:1), (13AS)-

Systematic Name

English

TETRAHYDROPALMATINE L-FORM HYDROCHLORIDE [MI]

Common Name

English

NSC-36363

Code

English

Code System Code Type Description

PUBCHEM

5351528