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
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
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: WP254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28721806 |
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Target ID: CHEMBL2056 |
124.0 nM [Ki] | ||
Target ID: CHEMBL217 |
388.0 nM [Ki] | ||
Target ID: CHEMBL3138 |
1.4 µM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
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 |
T1/2
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: Page: p.7, 8 |
healthy, ADULT n = 11 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: Page: p.7, 8 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
moderate [IC50 20.9 uM] | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
weak [IC50 48.6 uM] | ||||
yes [IC50 2.65 uM] | ||||
yes [Ki 6.42 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
DL-tetrahydropalmatine-produced hypotension and bradycardia in rats through the inhibition of central nervous dopaminergic mechanisms. | 1995 Oct |
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[Comparison of pharmacokinetics of tetrahydropalmatine monomer and extractive of corydalis and corydalis processed with vinegar]. | 2007 Dec |
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[Effects of rotundine injection on nitric oxide synthase in tissues of different organs after ischemia/reperfusion of brain in rats]. | 2007 Jun |
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[Difference absorption of l-tetrahydropalmatine and dl-tetrahydropalmatine in intestine of rats]. | 2007 May |
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Molecular cloning and characterization of tetrahydroprotoberberine cis-N-methyltransferase, an enzyme involved in alkaloid biosynthesis in opium poppy. | 2007 May 18 |
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[Optimal extraction of Dingxiang jiangqi granules]. | 2007 Nov |
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Levo-tetrahydropalmatine inhibits cocaine's rewarding effects: experiments with self-administration and brain-stimulation reward in rats. | 2007 Nov |
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Determination of tetrandrine and fangchinoline in plasma samples using hollow fiber liquid-phase microextraction combined with high-performance liquid chromatography. | 2007 Sep 14 |
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Comparative studies on pharmacokinetic fates of tetrahydropalmatine enantiomers in different chemical environments in rats. | 2008 Feb |
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Medication of l-tetrahydropalmatine significantly ameliorates opiate craving and increases the abstinence rate in heroin users: a pilot study. | 2008 Jul |
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[Studies on active ingredients in Corydalis, broken cell wall corydalis and its processed products]. | 2008 Jun |
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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 |
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[Pharmacokinetic studies of tetrahydropalmatine and dehydrocorydaline in rat after oral administration of yanhusuo extraction by LC-MS/MS method]. | 2008 Nov |
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One-step purification of palmatine and its derivative dl-tetrahydropalmatine from Enantia chlorantha using high-performance displacement chromatography. | 2008 Oct 24 |
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Isoquinoline alkaloids isolated from Corydalis yanhusuo and their binding affinities at the dopamine D1 receptor. | 2008 Sep 25 |
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Investigation of modulation of the alpha-2 receptor in tetrahydropalmatine (THP) analgesia in male Sprague-Dawley rats. | 2009 |
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Amphiphilic poly{[alpha-maleic anhydride-omega-methoxy-poly(ethylene glycol)]-co-(ethyl cyanoacrylate)} graft copolymer nanoparticles as carriers for transdermal drug delivery. | 2009 |
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Cytotoxic activity of alkaloids isolated from Stephania rotunda [corrected]. | 2009 Apr |
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Phytochemicals from Flemingia vestita (Fabaceae) and Stephania glabra (Menispermeaceae) alter cGMP concentration in the cestode Raillietina echinobothrida. | 2009 Apr |
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[Chemical constituents from Corydalis yanhusuo]. | 2009 Aug |
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Simultaneous determination of tetrahydropalmatine, protopine, and palmatine in rat plasma by LC-ESI-MS and its application to a pharmacokinetic study. | 2009 Feb 20 |
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Levo-tetrahydropalmatine attenuates oxycodone-induced conditioned place preference in rats. | 2009 Jan 14 |
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[Interaction between four herb compounds and a western drug by CYP3A4 enzyme metabolism in vitro]. | 2009 Jul |
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[Comparison of microwave-assisted and conventional extraction of Corydalis yanhusuo]. | 2009 Jul |
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[Study on the influence on Rhizoma Corydalis by different harvest time and processing methods]. | 2009 Jul |
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[Influence of combination of extractum Angelicae Dahuricae Siccum and total alkaloids of Rhizoma Corydalis on pharmacokinetics of tetrahydropalmatine in rats]. | 2009 Jun |
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[Pharmacokinetics of three alkaloids in Huanglianjiedu decoction in rat serum by LC-MS-MS]. | 2009 May |
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Purification of alkaloids from Corydalis yanhusuo W. T. Wang using preparative 2-D HPLC. | 2009 May |
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[Evaluation of different combinations of components of Chinese formulation shuangshentongguan by using AUC values]. | 2009 Sep |
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Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi) - validation of the Ayurvedic pharmacology through experimental and clinical studies. | 2010 Apr |
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Shotgun approach based comparative proteomic analysis of levo-tetrahydropalmatine-induced apoptosis in hepatocytes. | 2010 Apr 15 |
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[Bio-activity evaluation of Qinlian Siwu decoction on inhibiting mice uterine contraction in vitro and its components analysis]. | 2010 Dec |
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Levo-tetrahydropalmatine attenuates cocaine self-administration under a progressive-ratio schedule and cocaine discrimination in rats. | 2010 Dec |
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[Comparison of pharmacokinetics about ermiao capsules and ermiao pellet]. | 2010 Feb |
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[Effects of four components of Rhizoma Corydalis on anoxia and peroxidation injuries in neonatal cardiomyocytes]. | 2010 Jan |
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Preparative separation of isoquinoline alkaloids from Stephania yunnanensis by pH-zone-refining counter-current chromatography. | 2010 Jul 1 |
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Protective effects of tetrahydropalmatine against gamma-radiation induced damage to human endothelial cells. | 2010 Jul 3 |
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Simultaneous HPLC determination of three bioactive alkaloids in the Asian medicinal plant Stephania rotunda. | 2010 Jun |
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Affinity capillary electrophoresis coupling with partial filling technique and field-amplified sample injection for enantioseparation and determination of DL-tetrahydropalmatine. | 2010 Jun |
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Stereoselective protein binding of tetrahydropalmatine enantiomers in human plasma, HSA, and AGP, but not in rat plasma. | 2010 Jun |
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Combined comparative and chemical proteomics on the mechanisms of levo-tetrahydropalmatine-induced antinociception in the formalin test. | 2010 Jun 4 |
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[In vitro O-demethylation of rotundine by recombinant human CYP isoenzymes]. | 2010 Mar |
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Screening of antinociceptive components in Corydalis yanhusuo W.T. Wang by comprehensive two-dimensional liquid chromatography/tandem mass spectrometry. | 2010 Mar |
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Study on the stereoselective excretion of tetrahydropalmatine enantiomers in rats and identification of in vivo metabolites by liquid chromatography-tandem mass spectrometry. | 2010 Mar |
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Correlation between synergistic action of Radix Angelica dahurica extracts on analgesic effects of Corydalis alkaloid and plasma concentration of dl-THP. | 2010 May 4 |
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Chemical fingerprint analysis of Phellodendri Amurensis Cortex by ultra performance LC/Q-TOF-MS methods combined with chemometrics. | 2010 Nov |
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Tetrahydropalmatine inhibits pro-inflammatory mediators in lipopolysaccharide-stimulated THP-1 cells. | 2010 Oct |
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Levo-tetrahydropalmatine retards the growth of ectopic endometrial implants and alleviates generalized hyperalgesia in experimentally induced endometriosis in rats. | 2011 Jan |
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Organic cation transporter 1 mediates the uptake of monocrotaline and plays an important role in its hepatotoxicity. | 2013 Sep 15 |
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Involvement of organic cation transporter 1 and CYP3A4 in retrorsine-induced toxicity. | 2014 Aug 1 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01631383
30 mg twice daily (7 total doses)
Route of Administration:
Oral
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100000127779
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M10630
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SUB33902
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TETRAHYDROPALMATINE
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DTXSID701020650
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C014215
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3X69CO5I79
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SUBSTANCE RECORD