Synonym name:
Catalogue No.: BP0517
Cas No.: 3520-14-7
Formula: C₂₁H₂₅NO₄
Mol Weight: 355.434
Botanical Source: Alkaloid from several Corydalis spp., Berberis tinctoria and Coptis tecta (Fumariaceae, Menispermaceae, Berberidaceae, Ranunculaceae)

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.

HPLC of D-Tetrahydropalmatine

HNMR of D-Tetrahydropalmatine

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

D-Tetrahydropalmatine (D-Tetrahydropalmatine, abbreviated as D-THP) is an important isoquinoline alkaloid, mainly isolated from plants of the Corydalis spp. genus. As one of the active ingredients in the traditional Chinese medicine Corydalis corydalis, dextrotetrahydroparmatine has a long history of application in the fields of Chinese medicine for analgesic and sedative purposes. In recent years, with the deepening of research in natural product pharmacology and neuropharmacology, dextrotetrahydrobamatine has become a hot topic in research on various neurological diseases such as analgesia, anti-anxiety, and neuroprotection, due to its unique dopamine receptor regulation and multi-target pharmacological activity.

This review aims to systematically summarize the chemical structure and physicochemical properties, plant origin, and extraction methods of dextrotetrahydropalmatine, focusing on its pharmacological activity and mechanism of action. Combining druggability parameters and pharmacokinetic characteristics, it explores its clinical application potential and future development directions. By comprehensively reviewing related research progress, it is hoped that theoretical basis and reference will be provided for the drug development and clinical translation of dextrantetrahydroparmatine.

Chemical structure and physicochemical properties

The chemical name of dextrotetrahydroparmatine is (R)-2,3,9,10-tetrahydro-7,8-dimethoxy-2-methyl-5H-benzo[d]isoquinoline, molecular formula C21H25NO4, and molecular weight 355.4340. Its structure belongs to the isoquinoline alkaloid, featuring a typical tetrahydroisoquinoline backbone and containing two methoxy substituents, giving it a certain degree of hydrophobicity and aromaticity.

In terms of physicochemical properties, dextrotetrahydropalmatine has a LogP value of 3.3789, indicating moderate lipid solubility and facilitating crossing of the blood-brain barrier (BBB). Its polar surface area (TPSA) is 40.16 Ų, and its lower polarity helps distribute the central nervous system. Low water solubility (0.0234 mg/mL) suggests limited solubility in the aqueous phase, which may affect oral bioavailability. In vitro safety evaluations showed that dextrotetrahydropalmatine does not inhibit hERG channels, and Ames-induced mutagenic tests were negative, indicating high safety and promising drug development potential.

Plant Origins and Extraction Methods

Dextrotetrahydropalmatine is mainly found in Corydalis species, such as Corydalis yanhusuo and Corydalis turtschaninovii. Corydalis is a plant in the papaveveraceae family, with its rhizomes rich in various isoquinoline alkaloids, among which dextrotetrahydropalmatine is particularly abundant.

The extraction method typically uses organic solvent extraction combined with column chromatography separation technology. The specific process includes:

1. Raw material processing: Crush the dried Corydalis rhizome to an appropriate particle size.
2. Solvent extraction: Multiple reflux extractions are performed using polar solvents mainly composed of ethanol or methanol, with extraction time and temperature optimized according to the process.
3. Crude extract concentration: Vacuum concentration removes solvent to obtain the crude extract.
4. Separation and purification: Separation is performed using silica gel column chromatography, reversed-phase high-performance liquid chromatography (RP-HPLC), and other methods to obtain high-purity dextrotetrahydropalmatine.
5. Structural identification: Confirm the structure using nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR).

In recent years, the application of ultrasound-assisted extraction, microwave-assisted extraction, and membrane separation technologies has gradually improved extraction efficiency and purity, providing technical support for industrial production.

Pharmacological activity research

The pharmacological activity of dextrotetrahydropalmatine is mainly concentrated in the central nervous system, with particularly analgesic, sedating, and anxiolytic effects being the most significant.

Analgesic effect

Numerous in vivo and in vivo experiments have shown that dextrotetrahydropalmatine has a significant analgesic effect. Its analgesic effect not only relieves acute pain but also effectively suppresses chronic and neuropathic pain. Classic hot plate tests, acetic acid torsion tests, and nerve injury models have all confirmed its analgesic activity.

Sedative, anti-anxiety

Dextetrahydropalmatine exerts sedative and anxiolytic effects by modulating dopamine receptors, especially D1 and D2 receptor subtypes. Animal experiments have shown that dextrotetrahydroparmatine can reduce spontaneous exercise and anxious behaviors, demonstrating a good central sedative effect.

Other pharmacological effects

In addition to its nervous system effects, dextrotetrahydroparmatine also exhibits anti-inflammatory, antioxidant, and neuroprotective effects. Some studies have indicated its inhibitory effect on organic cation transporter 1 (OCT1), which may affect drug metabolism and transport, posing potential risks of drug interactions.

Mechanism of action and molecular targets

The pharmacological mechanism of dextrotetrahydrobamatine is complex, involving multiple neurotransmitter systems and ion channels.

Dopamine receptor regulation

As a dopamine receptor antagonist, dextetrahydroparmatine exhibits a selective affinity for D1 receptors and also has some antagonistic effects on D2 receptors. By blocking dopamine signaling, it regulates the excitability of the central nervous system, exerting sedative and analgesic effects.

Ion channel and receptor regulation

Research shows that dextrotetrahydropalmatine can regulate various ion channels and receptors, including:

• TRPV1 and TRPA1: These two transient receptor potential pathways are involved in pain and inflammation signaling, and the regulation of dextrotetrahydroparmatine helps alleviate pain and inflammation responses.
• CNR1 (Cannabinoid Receptor 1): Involved in neuroprotective and analgesic mechanisms, dextrotetrahydroparmatine may act by indirectly modulating the CNR1 signaling pathway.
• OPRD1, OPRM1, OPRK1 (δ, μ, κ-type opioid receptors): The effects of dextrantetrahydroparmatine on opioid receptors suggest that its analgesic effect may involve regulation of the endogenous opioid system.
• PTGS1 and PTGS2 (cyclooxygenases 1 and 2): As key enzymes in inflammatory mediator synthesis, dextrotetrahydroparmatine inhibits them and helps alleviate inflammation-related pain.
• SLC6A4 (5-hydroxytryptamine transporter): Its regulation may be related to the anti-anxiety and mood-stabilizing effects of dextrotetrahydroparmatine.

Inhibition of organic cation transporter 1 (OCT1).

Dextetrahydroparmatine is an effective OCT1 inhibitor that affects the uptake of various organic cations by the liver and kidneys, potentially regulating drug absorption, distribution, and metabolism, indicating its important role in drug interactions.

Druggability evaluation and pharmacokinetics

Druggability parameters

The molecular weight of dextrotetrahydropalmatine is 355.4340, meeting the molecular weight requirements of the Lipinski rule. The LogP is 3.3789, indicating good lipid solubility and favorable blood-brain barrier penetration (BBB); its TPSA is 40.16 Ų, with moderate polarity, meeting the ideal polarity range for central nervous system drugs. Low water solubility suggests that oral formulations need to optimize their solubility to improve bioavailability.

In terms of safety, dextrotetrahydroparmatine does not inhibit hERG channels, reducing the risk of cardiotoxicity; The Ames test was negative, indicating no significant mutagenicity and relatively high safety.

Pharmacokinetic characteristics

Animal experiments and preclinical studies show that dextrotetrahydropalmatine is rapidly absorbed orally, with a high peak plasma concentration (Cmax) and wide distribution, especially high concentrations in brain tissue, confirming its excellent blood-brain barrier penetration. It has a moderate half-life, with metabolism mainly via the hepatic CYP450 enzyme system, and metabolites primarily excreted through urine and bile.

Additionally, dextrotetrahydropalmatine's inhibitory effect on OCT1 may affect its own and other drug transport and metabolism, suggesting that potential drug interactions should be considered in clinical practice.

Prospects and outlooks for clinical applications

As a naturally derived multi-target central nervous system active compound, dextetrahydroparmatine has broad clinical application potential. Its analgesic, sedating, and anti-anxiety effects make it highly valuable in pain management and the treatment of neuropsychiatric disorders.

Currently, dextrantetrahydropalmatine is used as an over-the-counter analgesic or adjunct therapy in some Asian countries. With further in-depth research into its pharmacological mechanisms and safety, more efficient and safe derivatives or compound formulations are expected to be developed in the future, expanding its indications to include neuropathic pain, depression, and Parkinson's disease.

Additionally, the characteristics of dextrotetrahydrobamatine as an OCT1 inhibitor provide new research directions for drug metabolism regulation and personalized medication. By integrating modern medicinal chemistry and pharmacological techniques, optimizing its pharmacokinetic properties and improving water solubility and bioavailability will further promote its clinical translation.

Future research should focus on:

• Long-term safety and toxicological evaluation of dextrotetrahydropalmatine;
• Precisely elucidates its multi-target mechanisms and signaling pathways;
• Drug interactions and personalized medication guidance;
• Development of novel delivery systems and dosage forms.

Conclusion

As a natural isoquinoline alkaloid with multi-target effects, dextrotetrahydropalmatine demonstrates broad clinical application prospects due to its excellent central nervous system activity and good safety. Its unique dopamine receptor antagonism and OCT1 inhibitory effects provide new ideas and strategies for pain relief and the treatment of neurological diseases. In the future, through in-depth pharmacological mechanism research, druggability optimization, and clinical evaluation, dextritetrahydroparmatine and its derivatives are expected to become a new generation of safe and effective neurological drugs, bringing great hope to patients.