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.COC1=CC=C2C[C@@H]3N(CCC4=CC(OC)=C(OC)C=C34)CC2=C1OC

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 156 Target ID: WP254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28721806	Activator 1447
Dopamine D1 receptor 106 Target ID: CHEMBL2056 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17361394 \| https://www.ncbi.nlm.nih.gov/pubmed/22300097	Antagonist 2849	124.0 nM [Ki]
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17361394 \| https://www.ncbi.nlm.nih.gov/pubmed/22300097	Antagonist 2849	388.0 nM [Ki]
Dopamine D3 receptor 97 Target ID: CHEMBL3138 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17361394 \| https://www.ncbi.nlm.nih.gov/pubmed/22300097	Binding Agent 1076	1.4 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 305 Sources: https://clinicaltrials.gov/ct2/show/NCT02118610	Primary	Phase II 1147	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 1147	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 1147	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	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27363313	Sources: https://pubmed.ncbi.nlm.nih.gov/27363313

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1057 CYP1A2 2153 CYP2C19 2057 MATE1 415 MRP1 116 CYP3A4/5 296 CYP2A6 879 CYP2E1 1060 OCT2 779 BCRP 910 P-gp 1741	CYP1A2 1197 CYP3A4/5 91 P-gp 2052

Drug as perpetrator

Target	Modality	Activity
MATE1 416	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/32389634/	moderate [IC50 20.9 uM]
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/	no
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2A6 911	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2C8 1117	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP3A4/5 357	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
MRP1 232	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/	no
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/	weak [IC50 48.6 uM]
OCT2 782	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/32389634/	yes [IC50 2.65 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23001793/	yes [Ki 6.42 uM]

Drug as victim

Target	Modality	Activity
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006929	no
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23001793/	yes
CYP3A4/5 91	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23001793/	yes

PubMed

Title	Date	PubMed
Involvement of organic cation transporter 1 and CYP3A4 in retrorsine-induced toxicity.	2014-08-01	24799337
Organic cation transporter 1 mediates the uptake of monocrotaline and plays an important role in its hepatotoxicity.	2013-09-15	23831208
Levo-tetrahydropalmatine retards the growth of ectopic endometrial implants and alleviates generalized hyperalgesia in experimentally induced endometriosis in rats.	2011-01	20884991
[Bio-activity evaluation of Qinlian Siwu decoction on inhibiting mice uterine contraction in vitro and its components analysis].	2010-12	21438408
Levo-tetrahydropalmatine attenuates cocaine self-administration under a progressive-ratio schedule and cocaine discrimination in rats.	2010-12	20816889
Chemical fingerprint analysis of Phellodendri Amurensis Cortex by ultra performance LC/Q-TOF-MS methods combined with chemometrics.	2010-11	21049522
Tetrahydropalmatine inhibits pro-inflammatory mediators in lipopolysaccharide-stimulated THP-1 cells.	2010-10	20828314
Protective effects of tetrahydropalmatine against gamma-radiation induced damage to human endothelial cells.	2010-07-03	20562023
Preparative separation of isoquinoline alkaloids from Stephania yunnanensis by pH-zone-refining counter-current chromatography.	2010-07-01	20570221
Combined comparative and chemical proteomics on the mechanisms of levo-tetrahydropalmatine-induced antinociception in the formalin test.	2010-06-04	20359166
Simultaneous HPLC determination of three bioactive alkaloids in the Asian medicinal plant Stephania rotunda.	2010-06	20614814
Affinity capillary electrophoresis coupling with partial filling technique and field-amplified sample injection for enantioseparation and determination of DL-tetrahydropalmatine.	2010-06	20564697
Stereoselective protein binding of tetrahydropalmatine enantiomers in human plasma, HSA, and AGP, but not in rat plasma.	2010-06	19927376
Correlation between synergistic action of Radix Angelica dahurica extracts on analgesic effects of Corydalis alkaloid and plasma concentration of dl-THP.	2010-05-04	20307640
Shotgun approach based comparative proteomic analysis of levo-tetrahydropalmatine-induced apoptosis in hepatocytes.	2010-04-15	20109541
Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi) - validation of the Ayurvedic pharmacology through experimental and clinical studies.	2010-04	20814526
[In vitro O-demethylation of rotundine by recombinant human CYP isoenzymes].	2010-03	21351505
Screening of antinociceptive components in Corydalis yanhusuo W.T. Wang by comprehensive two-dimensional liquid chromatography/tandem mass spectrometry.	2010-03	20101504
Study on the stereoselective excretion of tetrahydropalmatine enantiomers in rats and identification of in vivo metabolites by liquid chromatography-tandem mass spectrometry.	2010-03	19544352
[Comparison of pharmacokinetics about ermiao capsules and ermiao pellet].	2010-02	20575422
[Effects of four components of Rhizoma Corydalis on anoxia and peroxidation injuries in neonatal cardiomyocytes].	2010-01	20349723
[Evaluation of different combinations of components of Chinese formulation shuangshentongguan by using AUC values].	2009-09	20055180
[Chemical constituents from Corydalis yanhusuo].	2009-08	19894534
[Interaction between four herb compounds and a western drug by CYP3A4 enzyme metabolism in vitro].	2009-07	19873787
[Comparison of microwave-assisted and conventional extraction of Corydalis yanhusuo].	2009-07	19873742
[Study on the influence on Rhizoma Corydalis by different harvest time and processing methods].	2009-07	19873726
[Influence of combination of extractum Angelicae Dahuricae Siccum and total alkaloids of Rhizoma Corydalis on pharmacokinetics of tetrahydropalmatine in rats].	2009-06	19806898
[Pharmacokinetics of three alkaloids in Huanglianjiedu decoction in rat serum by LC-MS-MS].	2009-05	19673395
Purification of alkaloids from Corydalis yanhusuo W. T. Wang using preparative 2-D HPLC.	2009-05	19347864
Cytotoxic activity of alkaloids isolated from Stephania rotunda [corrected].	2009-04	19107844
Phytochemicals from Flemingia vestita (Fabaceae) and Stephania glabra (Menispermeaceae) alter cGMP concentration in the cestode Raillietina echinobothrida.	2009-04	18854226
Simultaneous determination of tetrahydropalmatine, protopine, and palmatine in rat plasma by LC-ESI-MS and its application to a pharmacokinetic study.	2009-02-20	19121909
Levo-tetrahydropalmatine attenuates oxycodone-induced conditioned place preference in rats.	2009-01-14	19071107
Investigation of modulation of the alpha-2 receptor in tetrahydropalmatine (THP) analgesia in male Sprague-Dawley rats.	2009	22435350
Amphiphilic poly{[alpha-maleic anhydride-omega-methoxy-poly(ethylene glycol)]-co-(ethyl cyanoacrylate)} graft copolymer nanoparticles as carriers for transdermal drug delivery.	2009	19918369
[Pharmacokinetic studies of tetrahydropalmatine and dehydrocorydaline in rat after oral administration of yanhusuo extraction by LC-MS/MS method].	2008-11	19239032
One-step purification of palmatine and its derivative dl-tetrahydropalmatine from Enantia chlorantha using high-performance displacement chromatography.	2008-10-24	18804774
Isoquinoline alkaloids isolated from Corydalis yanhusuo and their binding affinities at the dopamine D1 receptor.	2008-09-25	18830156
Medication of l-tetrahydropalmatine significantly ameliorates opiate craving and increases the abstinence rate in heroin users: a pilot study.	2008-07	18565275
[Studies on active ingredients in Corydalis, broken cell wall corydalis and its processed products].	2008-06	18831201
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.	2008-03-01	18258496
Comparative studies on pharmacokinetic fates of tetrahydropalmatine enantiomers in different chemical environments in rats.	2008-02	18074336
[Comparison of pharmacokinetics of tetrahydropalmatine monomer and extractive of corydalis and corydalis processed with vinegar].	2007-12	18422179
[Optimal extraction of Dingxiang jiangqi granules].	2007-11	18309666
Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats.	2007-11	17888459
Determination of tetrandrine and fangchinoline in plasma samples using hollow fiber liquid-phase microextraction combined with high-performance liquid chromatography.	2007-09-14	17675049
[Effects of rotundine injection on nitric oxide synthase in tissues of different organs after ischemia/reperfusion of brain in rats].	2007-06	17577446
Molecular cloning and characterization of tetrahydroprotoberberine cis-N-methyltransferase, an enzyme involved in alkaloid biosynthesis in opium poppy.	2007-05-18	17389594
[Difference absorption of l-tetrahydropalmatine and dl-tetrahydropalmatine in intestine of rats].	2007-05	17703779
DL-tetrahydropalmatine-produced hypotension and bradycardia in rats through the inhibition of central nervous dopaminergic mechanisms.	1995-10	8577817

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 `Mon Mar 31 22:06:04 GMT 2025` Edited by `admin` on `Mon Mar 31 22:06:04 GMT 2025`
Record UNII	RH72T8K75E
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TETRAHYDROPALMATINE HYDROCHLORIDE

Common Name

English

NSC-36363

Preferred 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

Code System Code Type Description

PUBCHEM

5351528