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 1404
Dopamine D1 receptor 98 Target ID: CHEMBL2056 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17361394 \| https://www.ncbi.nlm.nih.gov/pubmed/22300097	Antagonist 2737	124.0 nM [Ki]
Dopamine D2 receptor 290 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17361394 \| https://www.ncbi.nlm.nih.gov/pubmed/22300097	Antagonist 2737	388.0 nM [Ki]
Dopamine D3 receptor 89 Target ID: CHEMBL3138 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17361394 \| https://www.ncbi.nlm.nih.gov/pubmed/22300097	Binding Agent 1037	1.4 µM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 288 Sources: https://clinicaltrials.gov/ct2/show/NCT02118610	Primary	Phase II 1133	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 1133	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 1133	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 1695	inhibitor 1789

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 869 CYP1A2 1463 CYP2C19 1410 MATE1 302 MRP1 106 CYP3A4/5 261 CYP2A6 670 CYP2E1 846 OCT2 630 BCRP 678 P-gp 1401	CYP1A2 1013 CYP3A4/5 82 P-gp 1491

Drug as perpetrator

Target	Modality	Activity
MATE1 304	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/32389634/	moderate [IC50 20.9 uM]
BCRP 751	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/	no
CYP1A2 1620	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2A6 702	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2C19 1484	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2C8 923	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2C9 1747	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP2E1 929	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
CYP3A4/5 314	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/ \| https://pubmed.ncbi.nlm.nih.gov/23001793/	no
MRP1 170	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/	no
P-gp 1588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/22900779/	weak [IC50 48.6 uM]
OCT2 631	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/32389634/	yes [IC50 2.65 uM]
CYP2D6 1826	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/23001793/	yes [Ki 6.42 uM]

Drug as victim

Target	Modality	Activity
P-gp 1491	substrate 3264 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174006929	no
CYP1A2 1013	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/23001793/	yes
CYP3A4/5 82	substrate 3264 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
Formation of protoberberine-type alkaloids by the tubers of somatic embryo-derived plants of Corydalis yanhusuo.	2001 Dec	11745021
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
Influence of light and heat on the stability of rotundine sulfate injection.	2001 Oct	11745708
The protective effect of dl-tetrahydropalmatine against the development of amygdala kindling seizures in rats.	2002 Mar 8	11852175
Positive cooperation of protoberberine type 2 alkaloids from Corydalis cava on the GABA(A) binding site.	2003 Apr	12709895
[Study on extraction conditions for minute powder of processed rhizome of Corydalis with vinegar].	2003 Oct	15620186
[Resource investigation and quality evaluation on wild Corydalis yanhusuo].	2004 May	15706885
[Stereoselective pharmacokinetics of tetrahydropalmatine in rats].	2005 Aug	16268511
A multidisciplinary approach to the toxicologic problems associated with the use of herbal medicines.	2005 Feb	15665747
[Chemical constituents from Corydalis humosa].	2005 Jul	16252721
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
Chiral high-performance liquid chromatographic separation of the enantiomers of tetrahydropalmatine and tetrahydroberberine, isolated from Corydalis yanhusuo.	2006 Feb	16402177
Evaluation of Cytotoxic Effects of Dichloromethane Extract of Guduchi (Tinospora cordifolia Miers ex Hook F & THOMS) on Cultured HeLa Cells.	2006 Jun	16786058
[Protective effect of dl-tetrahydropalmatine on liver injury induced by carbon tetrachloride in mice].	2006 Mar	16722379
[Effects of different types and standard of processing vinegaron inherent constituents in rhizoma of Corydalis yanhusuo].	2006 Mar	16722373
Enantioseparation of tetrahydropalmatine and Tröger's base by molecularly imprinted monolith in capillary electrochromatography.	2007 Feb 23	16978700
Characterization of enantioselective binding of racemic natural tetrahydropalmatine to DNA by chromatographic methods.	2007 Jan 1	16931189
[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
Antimalarial activity of alkaloids isolated from Stephania rotunda.	2007 May 30	17382502
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
[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
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
[Interaction between four herb compounds and a western drug by CYP3A4 enzyme metabolism in vitro].	2009 Jul	19873787
[Influence of combination of extractum Angelicae Dahuricae Siccum and total alkaloids of Rhizoma Corydalis on pharmacokinetics of tetrahydropalmatine in rats].	2009 Jun	19806898
[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
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
Affinity capillary electrophoresis coupling with partial filling technique and field-amplified sample injection for enantioseparation and determination of DL-tetrahydropalmatine.	2010 Jun	20564697
Organic cation transporter 1 mediates the uptake of monocrotaline and plays an important role in its hepatotoxicity.	2013 Sep 15	23831208

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