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

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
DL-tetrahydropalmatine-produced hypotension and bradycardia in rats through the inhibition of central nervous dopaminergic mechanisms.	1995 Oct	8577817
[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
[Difference absorption of l-tetrahydropalmatine and dl-tetrahydropalmatine in intestine of rats].	2007 May	17703779
Molecular cloning and characterization of tetrahydroprotoberberine cis-N-methyltransferase, an enzyme involved in alkaloid biosynthesis in opium poppy.	2007 May 18	17389594
[Optimal extraction of Dingxiang jiangqi granules].	2007 Nov	18309666
Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats.	2007 Nov	17888459
Determination of tetrandrine and fangchinoline in plasma samples using hollow fiber liquid-phase microextraction combined with high-performance liquid chromatography.	2007 Sep 14	17675049
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
[Studies on active ingredients in Corydalis, broken cell wall corydalis and its processed products].	2008 Jun	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 Mar 1	18258496
[Pharmacokinetic studies of tetrahydropalmatine and dehydrocorydaline in rat after oral administration of yanhusuo extraction by LC-MS/MS method].	2008 Nov	19239032
One-step purification of palmatine and its derivative dl-tetrahydropalmatine from Enantia chlorantha using high-performance displacement chromatography.	2008 Oct 24	18804774
Isoquinoline alkaloids isolated from Corydalis yanhusuo and their binding affinities at the dopamine D1 receptor.	2008 Sep 25	18830156
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
Cytotoxic activity of alkaloids isolated from Stephania rotunda [corrected].	2009 Apr	19107844
Phytochemicals from Flemingia vestita (Fabaceae) and Stephania glabra (Menispermeaceae) alter cGMP concentration in the cestode Raillietina echinobothrida.	2009 Apr	18854226
[Chemical constituents from Corydalis yanhusuo].	2009 Aug	19894534
Simultaneous determination of tetrahydropalmatine, protopine, and palmatine in rat plasma by LC-ESI-MS and its application to a pharmacokinetic study.	2009 Feb 20	19121909
Levo-tetrahydropalmatine attenuates oxycodone-induced conditioned place preference in rats.	2009 Jan 14	19071107
[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
[Influence of combination of extractum Angelicae Dahuricae Siccum and total alkaloids of Rhizoma Corydalis on pharmacokinetics of tetrahydropalmatine in rats].	2009 Jun	19806898
[Pharmacokinetics of three alkaloids in Huanglianjiedu decoction in rat serum by LC-MS-MS].	2009 May	19673395
Purification of alkaloids from Corydalis yanhusuo W. T. Wang using preparative 2-D HPLC.	2009 May	19347864
[Evaluation of different combinations of components of Chinese formulation shuangshentongguan by using AUC values].	2009 Sep	20055180
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
[Bio-activity evaluation of Qinlian Siwu decoction on inhibiting mice uterine contraction in vitro and its components analysis].	2010 Dec	21438408
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
Stereoselective protein binding of tetrahydropalmatine enantiomers in human plasma, HSA, and AGP, but not in rat plasma.	2010 Jun	19927376
Combined comparative and chemical proteomics on the mechanisms of levo-tetrahydropalmatine-induced antinociception in the formalin test.	2010 Jun 4	20359166
[In vitro O-demethylation of rotundine by recombinant human CYP isoenzymes].	2010 Mar	21351505
Screening of antinociceptive components in Corydalis yanhusuo W.T. Wang by comprehensive two-dimensional liquid chromatography/tandem mass spectrometry.	2010 Mar	20101504
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
Levo-tetrahydropalmatine retards the growth of ectopic endometrial implants and alleviates generalized hyperalgesia in experimentally induced endometriosis in rats.	2011 Jan	20884991
Organic cation transporter 1 mediates the uptake of monocrotaline and plays an important role in its hepatotoxicity.	2013 Sep 15	23831208
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.

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