TETRAHYDROPALMATINE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H25NO4
Molecular Weight	355.4275
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC3=C(CN1CCC4=C2C=C(OC)C(OC)=C4)C(OC)=C(OC)C=C3

InChI

InChIKey=AEQDJSLRWYMAQI-KRWDZBQOSA-N

InChI=1S/C21H25NO4/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/t17-/m0/s1

HIDE SMILES / InChI

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 153 Target ID: WP254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28721806	Activator 1410
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 2760	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 2760	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 1059	1.4 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 295 Sources: https://clinicaltrials.gov/ct2/show/NCT02118610	Primary	Phase II 1144	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 1144	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 1144	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 1752	inhibitor 1837

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 901 CYP1A2 1509 CYP2C19 1463 MATE1 304 MRP1 106 CYP3A4/5 273 CYP2A6 704 CYP2E1 876 OCT2 638 BCRP 691 P-gp 1437	CYP1A2 1032 CYP3A4/5 85 P-gp 1527

Drug as perpetrator

Target	Modality	Activity
MATE1 306	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/32389634/	moderate [IC50 20.9 uM]
BCRP 765	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/	no
CYP1A2 1673	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2A6 736	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2C19 1537	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2C8 955	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2C9 1803	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2E1 964	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP3A4/5 330	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
MRP1 172	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/	no
P-gp 1626	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/	weak [IC50 48.6 uM]
OCT2 639	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/32389634/	yes [IC50 2.65 uM]
CYP2D6 1875	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/23001793/	yes [Ki 6.42 uM]

Drug as victim

Target	Modality	Activity
P-gp 1527	substrate 3326 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006929	no
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/23001793/	yes
CYP3A4/5 85	substrate 3326 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
HIV-1 and HIV-2 reverse transcriptases: a comparative study of sensitivity to inhibition by selected natural products.	1992 May 29	1376118
DL-tetrahydropalmatine-produced hypotension and bradycardia in rats through the inhibition of central nervous dopaminergic mechanisms.	1995 Oct	8577817
DL-Tetrahydropalmatine may act through inhibition of amygdaloid release of dopamine to inhibit an epileptic attack in rats.	2001 Jul 20	11438389
The hypothermic effects of dl-tetrahydropalmatine in rats.	2001 Nov 23	11711213
Anxiolytic-like action of orally administered dl-tetrahydropalmatine in elevated plus-maze.	2003 Aug	12921909
[Study on extraction conditions for minute powder of processed rhizome of Corydalis with vinegar].	2003 Oct	15620186
Stereoselective pharmacokinetics of tetrahydropalmatine after oral administration of (-)-enantiomer and the racemate.	2005 May 15	15846827
[Studies on the alkaloids from herb of Corydalis adunca].	2005 Nov	16468373
Asymmetric synthesis of tetrahydropalmatine via tandem 1,2-addition/cyclization.	2005 Nov 11	16268624
Chiral liquid chromatography resolution and stereoselective pharmacokinetic study of tetrahydropalmatine enantiomers in dogs.	2005 Nov 5	16165405
Chiral high-performance liquid chromatographic separation of the enantiomers of tetrahydropalmatine and tetrahydroberberine, isolated from Corydalis yanhusuo.	2006 Feb	16402177
Determination of DL-tetrahydropalmatine in Corydalis yanhusuo by L-tetrahydropalmatine imprinted monolithic column coupling with reversed-phase high performance liquid chromatography.	2006 Jun 9	16603171
[Effects of different types and standard of processing vinegaron inherent constituents in rhizoma of Corydalis yanhusuo].	2006 Mar	16722373
[Comparison of pharmacokinetics of tetrahydropalmatine monomer and extractive of corydalis and corydalis processed with vinegar].	2007 Dec	18422179
[Effects of rotundine injection on nitric oxide synthase in tissues of different organs after ischemia/reperfusion of brain in rats].	2007 Jun	17577446
Molecular cloning and characterization of tetrahydroprotoberberine cis-N-methyltransferase, an enzyme involved in alkaloid biosynthesis in opium poppy.	2007 May 18	17389594
Antimalarial activity of alkaloids isolated from Stephania rotunda.	2007 May 30	17382502
[Optimal extraction of Dingxiang jiangqi granules].	2007 Nov	18309666
Comparative studies on pharmacokinetic fates of tetrahydropalmatine enantiomers in different chemical environments in rats.	2008 Feb	18074336
Medication of l-tetrahydropalmatine significantly ameliorates opiate craving and increases the abstinence rate in heroin users: a pilot study.	2008 Jul	18565275
Simultaneous determination of berberine, palmatine and jatrorrhizine by liquid chromatography-tandem mass spectrometry in rat plasma and its application in a pharmacokinetic study after oral administration of coptis-evodia herb couple.	2008 Mar 1	18258496
Isoquinoline alkaloids isolated from Corydalis yanhusuo and their binding affinities at the dopamine D1 receptor.	2008 Sep 25	18830156
Cytotoxic activity of alkaloids isolated from Stephania rotunda [corrected].	2009 Apr	19107844
Levo-tetrahydropalmatine attenuates oxycodone-induced conditioned place preference in rats.	2009 Jan 14	19071107
[Comparison of microwave-assisted and conventional extraction of Corydalis yanhusuo].	2009 Jul	19873742
[Pharmacokinetics of three alkaloids in Huanglianjiedu decoction in rat serum by LC-MS-MS].	2009 May	19673395
Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi) - validation of the Ayurvedic pharmacology through experimental and clinical studies.	2010 Apr	20814526
Shotgun approach based comparative proteomic analysis of levo-tetrahydropalmatine-induced apoptosis in hepatocytes.	2010 Apr 15	20109541
Levo-tetrahydropalmatine attenuates cocaine self-administration under a progressive-ratio schedule and cocaine discrimination in rats.	2010 Dec	20816889
[Comparison of pharmacokinetics about ermiao capsules and ermiao pellet].	2010 Feb	20575422
[Effects of four components of Rhizoma Corydalis on anoxia and peroxidation injuries in neonatal cardiomyocytes].	2010 Jan	20349723
Preparative separation of isoquinoline alkaloids from Stephania yunnanensis by pH-zone-refining counter-current chromatography.	2010 Jul 1	20570221
Protective effects of tetrahydropalmatine against gamma-radiation induced damage to human endothelial cells.	2010 Jul 3	20562023
Simultaneous HPLC determination of three bioactive alkaloids in the Asian medicinal plant Stephania rotunda.	2010 Jun	20614814
Affinity capillary electrophoresis coupling with partial filling technique and field-amplified sample injection for enantioseparation and determination of DL-tetrahydropalmatine.	2010 Jun	20564697
Combined comparative and chemical proteomics on the mechanisms of levo-tetrahydropalmatine-induced antinociception in the formalin test.	2010 Jun 4	20359166
Study on the stereoselective excretion of tetrahydropalmatine enantiomers in rats and identification of in vivo metabolites by liquid chromatography-tandem mass spectrometry.	2010 Mar	19544352
Correlation between synergistic action of Radix Angelica dahurica extracts on analgesic effects of Corydalis alkaloid and plasma concentration of dl-THP.	2010 May 4	20307640
Chemical fingerprint analysis of Phellodendri Amurensis Cortex by ultra performance LC/Q-TOF-MS methods combined with chemometrics.	2010 Nov	21049522
Tetrahydropalmatine inhibits pro-inflammatory mediators in lipopolysaccharide-stimulated THP-1 cells.	2010 Oct	20828314
Involvement of organic cation transporter 1 and CYP3A4 in retrorsine-induced toxicity.	2014 Aug 1	24799337

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 `Thu Jul 06 02:52:54 UTC 2023` Edited by `admin` on `Thu Jul 06 02:52:54 UTC 2023`
Record UNII	3X69CO5I79
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TETRAHYDROPALMATINE

Common Name

English

LEVO-TETRAHYDROPALMATINE

Common Name

English

5,8,13,13A-TETRAHYDRO-(S)-2,3,9,10-TETRAMETHOXY-6H-DIBENZO(A,G)QUINOLIZINE

Common Name

English

(-)-ROTUNDINE

Common Name

English

ROTUNDINE

Common Name

English

TETRAHYDROPALMATINE, L-

Common Name

English

CASEANINE

Common Name

English

(-)-TETRAHYDROPALMATINE

Common Name

English

GINDARINE

Common Name

English

TETRAHYDROPALMATINE, (-)-

Common Name

English

(-)-CORYDALIS B

Common Name

English

(-)-2,3,9,10-TETRAMETHOXYBERBINE

Systematic Name

English

TETRAHYDROPALMATINE L-FORM [MI]

Common Name

English

HYNDARINE

Common Name

English

Tetrahydropalmatine [WHO-DD]

Common Name

English

2,3,9,10-TETRAMETHOXYBERBINE

Systematic Name

English

Code System Code Type Description

CAS

483-14-7