(R)-Tetrahydropapaverine HCl is the inactive isomer of Tetrahydropapaverine HCl and could be utilized as a control compound in experiments. Tetrahydropapaverine HCl is one of the active molecules of tetrahydroisoquinolines. Tetrahydropapaverine HCl has neurotoxic effects on dopamine neurons.

Physicochemical Properties

Molecular Formula	C20H26CLNO4
Molecular Weight	379.88
Exact Mass	379.155
CAS #	54417-53-7
Related CAS #	Tetrahydropapaverine hydrochloride;6429-04-5
PubChem CID	44891027
Appearance	Typically exists as solid at room temperature
Density	1.12 g/cm3
Boiling Point	475.8ºC at 760 mmHg
Flash Point	202.7ºC
Index of Refraction	1.549
LogP	4.281
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	6
Heavy Atom Count	26
Complexity	407
Defined Atom Stereocenter Count	1
SMILES	COC1=C(C=C(C=C1)C[C@@H]2C3=CC(=C(C=C3CCN2)OC)OC)OC.Cl
InChi Key	VMPLLPIDRGXFTQ-PKLMIRHRSA-N
InChi Code	InChI=1S/C20H25NO4.ClH/c1-22-17-6-5-13(10-18(17)23-2)9-16-15-12-20(25-4)19(24-3)11-14(15)7-8-21-16;/h5-6,10-12,16,21H,7-9H2,1-4H3;1H/t16-;/m1./s1
Chemical Name	(1R)-1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline;hydrochloride
Synonyms	54417-53-7; R-tetrahydropapaverine HCl; (R)-(-)-Norlaudanosine hydrochloride; (r)-1-(3,4-dimethoxy-benzyl)-6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline hydrochloride; (R)-1-(3,4-Dimethoxy-benzyl)-6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline HCl; (r)-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride; (R)-Tetrahydropapaverine (hydrochloride); (R)-1,2,3,4-tetrahydro-6,7-dimethoxy-1-veratrylisoquinoline 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
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

ln Vitro	The inhibitory effects of tetrahydropapaverine on serotonin biosynthesis in serotonin-producing murine mastocytoma P815 cells were investigated. Tetrahydropapaverine at concentration ranges of 5-20 microM decreased serotonin content in a concentration-dependent manner in P815 cells and showed 42.1% inhibition of serotonin content at 5.0 microM at 24 hr. The value of 50% inhibitory concentration, IC50, of tetrahydropapaverine was 6.2 microM. Under these conditions, tryptophan hydroxylase (EC 1.14.16.4, TPH) was inhibited for 24-36 hr after treatment with tetrahydropapaverine in P815 cells (49.1% inhibition at 7.5 microM). However, aromatic L-amino acid decarboxylase activity was not affected by tetrahydropapaverine. In addition, tetrahydropapaverine inhibited the activity of TPH, prepared from the P815 cells (P815-TPH), with the IC50 value of 5.7 microM. Tetrahydropapaverine un-competitively inhibited P815-TPH with the substrate L-tryptophan, and non-competitively with the cofactor DL-6-methyl-5,6,7,8-tetrahydropteridin. The Ki value of tetrahydropapaverine with L-tryptophan was 10.1 microM. These data indicate that tetrahydropapaverine leads to a decrease in serotonin content by the inhibition of TPH activity in P815 cells. [2]
ln Vivo	Researchers report the toxic effects of 3,4-dimethoxyphenylethylamine (DMPEA), and tetrahydropapaverine (THP) on the rat nigrostriatal system; THP is a tetrahydroisoquinoline compound which may be derived from DMPEA by conjugation of DMPEA and its oxidative metabolite, dimethoxyphenylacetaldehyde; both are potent inhibitors of mitochondrial complex I. These compounds were introduced to the unilateral caudate-putamen of male Sprague-Dawley rats over 7 days using a 200-microl mini-osmotic pump. Striatal dopamine on the injected side showed a significant decrease to 86% of the non-injected side after 16.55 micromol/7 days infusion of DMPEA, and to 73% of the non-injected side after 7.90 micromol/7 days of THP infusion; as the non-injected side dopamine also reduced in the THP-injected rats, dopamine on the injected side was 55% of the saline control. Tyrosine hydroxylase (TH)-positive nigral neurons were decreased to 76% of the non-injected side after 16.55 micromol/7 days infusion of DMPEA and to 77% after 7.90 micromol/7 days of THP infusion. Dimethoxyphenyl-tetrahydroisoquinoline compounds appear to be potent nigral neurotoxins. [1]
Cell Assay	The treatment of P815 cells with tetrahydropapaverine significantly reduced the intracellular serotonin content in a concentration-dependent manner. Tetrahydropapaverine decreased serotonin content by 57.9% at a concentration of 5.0 μM (Table 1). The IC50 value of tetrahydropapaverine was 6.2 μM (Table 1). Under these conditions, the intracellular TPH activity was significantly inhibited by the treatment with tetrahydropapaverine (49.1% inhibition at 7.5 μM) while AADC activity was not affected...[2]
References	[1]. Koshimura I, et al. Dimethoxyphenylethylamine and tetrahydropapaverine are toxic to the nigrostriatal system. Brain Res. 1997 Oct 31;773(1-2):108-16. [2]. Kim EI, et al. Inhibitory effects of tetrahydropapaverine on serotonin biosynthesis in murine mastocytoma P815 cells. Life Sci. 2004 Sep 3;75(16):1949-57.
Additional Infomation	Tetrahydroisoquinolines (TIQs) have been extensively studied to have a neurotoxic activity (Nagatsu, 1997) and an inhibitory effect on dopamine biosynthesis (Kim et al., 2001, Shih et al., 1999). TIQs are also structurally similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which causes a Parkinson-like syndrome in human and non-human primates (McNaught et al., 1998). Among TIQs, salsolinol and tetrahydropapaveroline have been identified in the urine of Parkinsonian patients receiving L-DOPA therapy (Sandler et al., 1973) (Fig. 1). Salsolinol has been found to inhibit the activities of tyrosine hydroxylase (EC 1.14.16.2), the rate-limiting enzyme of catecholamine biosynthetic pathway (Minami et al., 1992) and TPH, the rate-limiting enzyme in serotonin biosynthesis (Ota et al., 1992). Tetrahydropapaveroline also inhibits the activity of tyrosine hydroxylase (Lee et al., 2001a). Recently, it is reported that tetrahydropapaveroline inhibits dopamine biosynthesis by the inhibition of tyrosine hydroxylase in PC12 cells (Lee et al., 2001a) and also reduces serotonin content by the inhibition of TPH in murine mastocytoma P815 cells (Kim et al., 2003). In addition, tetrahydropapaveroline has been proven to non-competitively inhibit TPH activity with the substrate L-tryptophan (Kim et al., 2003). Tetrahydropapaverine, one of the TIQs and an analogue of salsolinol and tetrahydropapaveroline, has been reported to have neurotoxic effects on dopamine neurons (Koshimura et al., 1997) (Fig. 1). However, the effects of tetrahydropapaverine on indoleamine biosynthesis or the metabolism of it have not been evaluated. The murine mastocytoma P815 cells are known to produce serotonin and to have a high TPH activity (Schindler et al., 1959). P815 cells also express histamine and L-histidine decarboxylase (Schindler et al., 1959, Imanishi et al., 1987). The present study was, therefore, undertaken to investigate the inhibitory effects of tetrahydropapaverine on serotonin biosynthesis in P815 cells and TPH activity. The enzyme source of TPH was prepared from the P815 cells (P815-TPH).[2]

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6324 mL	13.1621 mL	26.3241 mL
	5 mM	0.5265 mL	2.6324 mL	5.2648 mL
	10 mM	0.2632 mL	1.3162 mL	2.6324 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.