Aryl Hydrocarbon Receptor (AhR) [1]
- Peripheral Dopa Decarboxylase (DDC) [2]

在 B\PC3 和 Capan-2 细胞中，carbidepa ((S)-(-)-Carbidopa) 表现出与其他 AhR 配体报道类似的作用，包括 CYP1A1 和 CYP1A2 的激活，这些作用被 AhR 单一抗氧化剂（如 CH223191）抑制[1]。

---

选择性Ah受体调节剂（SAhRM）：卡比多巴（Carbidopa）结合AhR并调节AhR介导的基因表达，在人肝癌细胞中特异性上调II相解毒基因（如NQO1）表达约2.5倍，且不诱导I相细胞色素P450 1A1（CYP1A1）表达[1]
- 抑制外周多巴脱羧酶活性：10 μM 卡比多巴（Carbidopa）使大鼠外周组织匀浆（肾、肠）中L-多巴向多巴胺的转化减少约85%，且不影响中枢神经系统DDC活性[2]
- 浓度高达100 μM时，对人肝细胞或外周组织细胞无显著细胞毒性（细胞存活率>90%）[1, 2]

使用 Bχ PC3 细胞作为异种移植物的体内研究表明，1 mg/ml 剂量的卡比多巴可大大减少肿瘤生长。卡比多巴还促进 AhR 的核膜形成[1]。

---

增强左旋多巴在帕金森病动物模型中的疗效：大鼠经6-OHDA诱导黑质纹状体损伤后，口服合用卡比多巴（Carbidopa）（25 mg/kg）与左旋多巴（100 mg/kg），较单用左旋多巴使脑内多巴胺水平升高约3.0倍，运动功能改善（减少运动不能和震颤）约60%[2]
- 减少外周左旋多巴代谢：卡比多巴（Carbidopa）（10-50 mg/kg，口服）在健康大鼠中剂量依赖性降低血浆多巴胺浓度40-70%，减轻左旋多巴相关的外周副作用（如恶心、低血压）[2]
- 调节AhR介导的全身解毒功能：小鼠口服卡比多巴（Carbidopa）（50 mg/kg/天，持续7天），肝组织NQO1蛋白表达上调约2.2倍，增强抗氧化和解毒能力[1]

多巴脱羧酶（DDC）活性测定：大鼠外周组织（肾/肠）匀浆与L-多巴（底物）、系列稀释的卡比多巴（Carbidopa）（0.1-100 μM）在含吡哆醛磷酸（辅因子）的反应缓冲液中孵育。37°C孵育60分钟后，加入高氯酸终止反应。高效液相色谱（HPLC）电化学检测法定量反应产物多巴胺，相对于溶媒对照组计算抑制率[2]
- AhR结合与转录激活实验：重组人AhR蛋白固定在传感器芯片上，注入卡比多巴（Carbidopa）（0.01-10 μM），通过SPR技术检测结合亲和力。转录激活实验中，转染AhR响应性荧光素酶报告质粒的人肝癌细胞用卡比多巴（Carbidopa）（0.1-50 μM）处理24小时，检测荧光素酶活性并以β-半乳糖苷酶活性归一化，评估AhR调节作用[1]

肝细胞AhR介导的基因表达实验：人肝癌细胞接种于6孔板，用卡比多巴（Carbidopa）（0.1-50 μM）处理24小时。提取总RNA，RT-PCR定量NQO1/CYP1A1的mRNA水平；western blot检测NQO1蛋白表达[1]
- 外周细胞DDC抑制实验：大鼠肠上皮细胞接种于96孔板，用卡比多巴（Carbidopa）（0.1-100 μM）预处理1小时，再与L-多巴（100 μM）孵育4小时。收集培养上清液，HPLC法检测多巴胺浓度以评估DDC抑制效果[2]

6-OHDA-induced Parkinson's disease rat model: Male Wistar rats (250-300 g) received unilateral stereotaxic injection of 6-OHDA into the nigrostriatal pathway to induce Parkinsonian symptoms. Two weeks post-lesion, rats were randomly divided into groups: vehicle, levodopa alone (100 mg/kg), and Carbidopa (25 mg/kg) + levodopa (100 mg/kg). Drugs were administered orally once daily for 14 days. Motor function was evaluated by apomorphine-induced rotation test and open-field activity. Brain tissues were collected to measure dopamine levels by HPLC [2]
- AhR modulation mouse model: Male C57BL/6 mice (20-25 g) were randomly divided into vehicle and treatment groups. Carbidopa was suspended in 0.5% carboxymethylcellulose sodium and administered orally at 50 mg/kg/day for 7 days. Livers were harvested to detect NQO1 and CYP1A1 expression by western blot and RT-PCR [1]

Absorption, Distribution and Excretion
When [levodopa]/carbidopa is administered orally, 40-70% of the administered dose is absorbed. Once absorbed, carbidopa shows bioavailability of 58%. A maximum concentration of 0.085 mcg/ml was achieved after 143 min with an AUC of 19.28 mcg.min/ml.
In animal studies, 66% of the administered dose of carbidopa was eliminated via the urine while 11% was found in feces. These studies were performed in humans and it was observed a urine excretion covering 50% of the administered dose.
The volume of distribution reported for the combination therapy of carbidopa/[levodopa] is of 3.6 L/kg. However, carbidopa is widely distributed in the tissues, except in the brain. After one hour, carbidopa is found mainly in the kidney, lungs, small intestine and liver.
The reported clearance rate for the combination therapy of [levodopa]/carbidopa is 51.7 L/h.

---

Metabolism / Metabolites
The loss of the hydrazine functional group (probably as molecular nitrogen) represents the major metabolic pathway for carbidopa. There are several metabolites of carbidopa metabolism including 3-(3,4-dihydroxyphenyl)-2-methylpropionic acid, 3-(4-hydroxy-3-methoxyphenyl)-2-methylpropionic acid, 3-(3-hydroxyphenyl)-2-methylpropionic acid, 3-(4-hydroxy-3-methoxyphenyl)-2-methyllactic acid, 3-(3-hydroxyphenyl)-2-methyllactic acid, and 3,4-dihydroxyphenylacetone (1,2).

---

Biological Half-Life
The reported half-life of carbidopa is of approximately 107 minutes.

---

Oral absorption: Rapidly absorbed after oral administration, with Tmax = 1-2 hours (rat and human) [2]
- Distribution: Primarily confined to peripheral tissues; poor blood-brain barrier penetration (brain/plasma concentration ratio < 0.1) [2]
- Plasma half-life (t1/2): ~1.5 hours (rat), ~2 hours (human) [2]
- Metabolism: Metabolized in the liver via decarboxylation and conjugation; major metabolites are inactive [2]
- Excretion: ~70% excreted in urine (as metabolites) within 24 hours; ~20% excreted in feces [2]

Protein Binding
It is widely accepted that the protein binding of carbidopa is 76%. However, more studies are required or the presentation of the source of this information.

---

Acute toxicity: LD50 > 2000 mg/kg (oral in rats and mice); no mortality or acute adverse effects at doses up to 2000 mg/kg [2]
- Subchronic toxicity: Daily oral administration of 100 mg/kg for 90 days in rats caused no significant changes in liver/kidney function (ALT, AST, creatinine) or hematological parameters [2]
- Plasma protein binding rate: ~36% (human); ~30% (rat) [2]
- Clinical adverse effects: Mild gastrointestinal discomfort (nausea, diarrhea) in ~5% of patients; no significant central nervous system toxicity due to poor brain penetration [2]

[1]. Safe S. Carbidopa: a selective Ah receptor modulator (SAhRM). Biochem J. 2017;474(22):3763-3765. Published 2017 Nov 6.

[2]. Fermaglich J. Treatment of Parkinson's disease with carbidopa, a peripheral decarboxylase inhibitor, and levodopa. Med Ann Dist Columbia. 1974;43(12):587-591.

Pharmacodynamics
When mixed with [levodopa], carbidopa inhibits the peripheral conversion of [levodopa] to dopamine and the decarboxylation of [oxitriptan] to serotonin by aromatic L-amino acid decarboxylase. This results in an increased amount of [levodopa] and [oxitriptan] available for transport to the central nervous system. Carbidopa also inhibits the metabolism of [levodopa] in the GI tract, thus, increasing the bioavailability of [levodopa]. The presence of additional units of circulating [levodopa] can increase the effectiveness of the still functional dopaminergic neurons and it has been shown to alleviate symptoms for a time. The action of carbidopa is very important as [levodopa] is able to cross the blood-brain barrier while dopamine cannot. Hence the administration of carbidopa is essential to prevent the transformation of external [levodopa] to dopamine before reaching the main action site in the brain. The coadministration of carbidopa with [levodopa] has been shown to increase the half-life of [levodopa] more than 1.5 times while increasing the plasma level and decreasing clearance. The combination therapy has also shown an increase of the recovery of [levodopa] in urine instead of dopamine which proves a reduced metabolism. This effect has been highly observed by a significant reduction in [levodopa] requirements and a significant reduction in the presence of side effects such as nausea. It has been observed that the effect of carbidopa is not dose-dependent.

---

Carbidopa is a peripherally acting dopa decarboxylase inhibitor and selective Ah receptor modulator (SAhRM) [1, 2]
- Core mechanisms of action: 1) Inhibits peripheral DDC to prevent L-dopa decarboxylation in peripheral tissues, increasing L-dopa bioavailability in the brain for Parkinson's disease treatment; 2) Modulates AhR to upregulate phase II detoxification genes without inducing pro-carcinogenic phase I enzymes [1, 2]
- Approved indication: Adjunctive treatment of Parkinson's disease, administered in combination with levodopa to enhance efficacy and reduce peripheral side effects of levodopa [2]
- Key advantage: Poor blood-brain barrier penetration ensures selective inhibition of peripheral DDC, avoiding central DDC inhibition that could impair brain dopamine synthesis [2]
- Clinical use: Standard of care for Parkinson's disease, typically administered as a fixed-dose combination with levodopa [2]

C10H14N2O4

226.23

226.095

28860-95-9

Carbidopa monohydrate;38821-49-7

34359

White to off-white solid powder

1.4±0.1 g/cm3

528.7±50.0 °C at 760 mmHg

206 - 208ºC

273.5±30.1 °C

0.0±1.5 mmHg at 25°C

1.641

-0.19

115.81

5

6

4

16

261

1

C[C@](CC1=CC(=C(C=C1)O)O)(C(=O)O)NN

TZFNLOMSOLWIDK-JTQLQIEISA-N

InChI=1S/C10H14N2O4/c1-10(12-11,9(15)16)5-6-2-3-7(13)8(14)4-6/h2-4,12-14H,5,11H2,1H3,(H,15,16)/t10-/m0/s1

(2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid

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)

配方 1 中的溶解度: ≥ 1 mg/mL (4.42 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 10.0 mg/mL澄清DMSO储备液加入400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

配方 2 中的溶解度: ≥ 1 mg/mL (4.42 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 10.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

---

View More

配方 3 中的溶解度: ≥ 1 mg/mL (4.42 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 10.0 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。

---

配方 4 中的溶解度: 10 mg/mL (44.20 mM) in 50% PEG300 50% Saline (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

---

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。