研究了四氢罂粟碱对产生血清素的小鼠肥大细胞瘤P815细胞血清素生物合成的抑制作用。四氢罂粟碱在5-20 μ m浓度范围内以浓度依赖的方式降低P815细胞血清素含量，在5.0 μ m浓度下，24小时血清素含量抑制率为42.1%。四氢罂粟碱50%抑制浓度（IC50）为6.2 μ m。在此条件下，四氢罂粟碱对P815细胞色氨酸羟化酶（EC 1.14.16.4， TPH）的抑制作用达到24-36小时（7.5 μ m时抑制49.1%）。而四氢罂粟碱对芳香族l -氨基酸脱羧酶活性没有影响。此外，四氢罂粟碱对P815细胞（P815-TPH）制备的TPH活性有抑制作用，IC50值为5.7 μ m。四氢罂粟碱与底物l-色氨酸无竞争性抑制P815-TPH，与辅因子dl -6-甲基-5,6,7,8-四氢罂粟碱无竞争性抑制P815-TPH。四氢罂粟碱与l -色氨酸的Ki值为10.1 μ m。这些数据表明，四氢罂粟碱通过抑制P815细胞的TPH活性导致血清素含量降低。［２］

研究人员报告了3,4-二甲氧基苯乙胺（DMPEA）和四氢罂粟碱（THP）对大鼠黑纹状体系统的毒性作用；THP是一种四氢异喹啉化合物，可由DMPEA及其氧化代谢物二甲氧基苯乙醛偶联而得；这两种化合物都是线粒体复合物i的有效抑制剂。这些化合物通过200微利微渗透泵注入雄性Sprague-Dawley大鼠单侧尾壳核7天。注射侧纹状体多巴胺在注射DMPEA 16.55微mol/7 d后显著降低至非注射侧的86%，注射7.90微mol/7 d后显著降低至非注射侧的73%；由于注射thp的大鼠未注射侧多巴胺也减少，注射侧多巴胺为生理盐水对照组的55%。DMPEA注射16.55微mol/7 d后，酪氨酸羟化酶（TH）阳性的黑质神经元减少到未注射侧的76%，THP注射7.90微mol/7 d后减少到77%。二甲氧基苯基-四氢异喹啉化合物似乎是强效的神经毒素。［1］

四氢罂粟碱处理P815细胞显著降低细胞内血清素含量呈浓度依赖性。在5.0 μM浓度下，四氢罂粟碱可使血清素含量降低57.9%（表1），IC50值为6.2 μM（表1）。在此条件下，四氢罂粟碱可显著抑制细胞内TPH活性（7.5 μM浓度下抑制49.1%），而AADC活性未受影响。［２］

[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.

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]

C20H26CLNO4

379.88

379.155

54417-53-7

Tetrahydropapaverine hydrochloride;6429-04-5

44891027

Typically exists as solid at room temperature

1.12 g/cm3

475.8ºC at 760 mmHg

202.7ºC

1.549

4.281

48.95

2

5

6

26

407

1

COC1=C(C=C(C=C1)C[C@@H]2C3=CC(=C(C=C3CCN2)OC)OC)OC.Cl

VMPLLPIDRGXFTQ-PKLMIRHRSA-N

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

(1R)-1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline;hydrochloride

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;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。