Tetrahydropalmatine (also known as DL-Tetrahydropalmatine) hydrochloride has analgesic properties. Tetrahydropalmatine hydrochloride prevents a rat epileptic seizure by blocking the release of dopamine from amygdaloid.

Physicochemical Properties

Molecular Formula	C21H26CLNO4
Molecular Weight	391.8884
Exact Mass	391.155
CAS #	6024-85-7
Related CAS #	Rotundine; 483-14-7; Tetrahydropalmatine; 2934-97-6
PubChem CID	6602555
Appearance	White to off-white solid powder
Boiling Point	482.9ºC at 760 mmHg
Melting Point	250-252ºC
Flash Point	138.7ºC
LogP	4.116
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	27
Complexity	475
Defined Atom Stereocenter Count	0
InChi Key	MGSZZQQRTPWMEI-UHFFFAOYSA-N
InChi Code	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
Chemical Name	2,3,9,10-tetramethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline;hydrochloride
Synonyms	Tetrahydropalmatine hydrochloride; DL-Tetrahydropalmatine hydrochloride
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Dopamine
ln Vitro	Tetrahydropalmatine suppresses the production of COX-2 protein and mRNA induced by LPS in a dose-dependent manner. It specifically inhibits the ERK1=2 and p38 MAPK signaling pathways and suppresses activation of the NF-kB signaling pathway, which regulates the expression of IL-8[1]. By downregulating XIAP protein and inhibiting MDM2 linked to a proteasome-dependent pathway, L-THP causes p53 independent apoptosis. It also increases the susceptibility of EU-4 cells to doxorubicin. Apoptosis is the result of caspase activation caused by L-THP[2]. Voltage-sensitive Ca2+ channels and dopamine D1 and D2 receptors are both blocked by l-THP[3].
ln Vivo	l-THP may reduce the effects of oxycodone on the locomotor system and prevent the emergence and manifestation of oxycodone behavioral sensitization[3].
Cell Assay	The MTT assay measures cell viability. THP-1 cells are essentially seeded in 96-well plates at a density of 5×104 cells/mL. There is a control group in every batch of cells that has not received treatment. Each well is then filled with tetrahydropalmatine (0.2, 1, or 2 mM) and LPS (2 mg/mL). The plates are then incubated for 24 hours at 37°C with 5% CO2 in the air. Samples are cultivated for an additional 4 hours after MTT solutions (5 mg/mL) are added to each well. Each well receives 100 mL of dimethylsulfoxide after the supernatant is discarded. The optical density at 590 nm is then measured.
Animal Protocol	Rats: In this study, male Sprague-Dawley rats weighing 250–320 g are employed. The animals live in a room with a controlled temperature of 22±1°C and a 12:12 h light/dark cycle. They have unlimited access to food and water. At 6:00 a.m., the light is turned on, and it turns off at 18:00 a.m. Study is done on at least two major animal groups. (1) Rats given a vehicle treatment got an intraperitoneal injection of 0.9% saline along with 3–4 mg/kg of picrotoxin. (2) Rats treated with tetrahydropalmatine receive an injection of both picrotoxin (3–4 mg/kg, s.c.) and tetrahydropalmatine (10 mg/kg, i.p.). Rats that are not sedated are used to evaluate the effects of intraperitoneal injection (s.c.) of picrotoxin or tetrahydropalmatine on locomotor activity. Conversely, urethane (1.4 g/kg, i.p.) anesthesia is used to evaluate the effects of picrotoxin or tetrahydropalmatine on amygdaloid DA release in rats. Nine groups of eight rats each are created by randomly selecting seventy-two unstimulated rats. The animals are given an injection of saline, tetrahydropalmatine (10 or 15 mg/kg, i.p. ), or picrotoxin (3 or 4 mg/kg, s.c.) after spending 30 minutes getting used to the behavior apparatus. The 30-minute period that follows the injections is then used to record the rats' locomotor activity.
References	[1]. J Med Food . 2010 Oct;13(5):1125-32. [2]. Curr Mol Med . 2017;17(3):236-245. [3]. Acta Pharmacol Sin . 2005 May;26(5):533-8.

Solubility Data

Solubility (In Vitro)

DMSO: 12~25 mg/mL (30.6~63.8 mM) H2O: ~4 mg/mL (~10.2 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (6.38 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.38 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.38 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5517 mL	12.7587 mL	25.5174 mL
	5 mM	0.5103 mL	2.5517 mL	5.1035 mL
	10 mM	0.2552 mL	1.2759 mL	2.5517 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.