在 CHO 细胞中，溴隐亭增加 D2 多巴胺受体的表达，然后与 [35S]-GTPγS 结合，pEC50 为 8.15±0.05[1]。另一种有效的脑一氧化氮合酶抑制剂是溴隐亭。结果表明，麦角生物碱溴隐亭（BKT）对诱导型巨噬细胞NOS作用较弱（IC50>100 μM），但它是纯神经元一氧化氮合酶（NOS）的有效抑制剂（IC50=10±2 μM）[2 ]。已发现至少一种人类细胞色素P450酶被溴隐亭抑制。强效 CYP3A4 抑制剂溴隐亭的相互作用 IC50 值为 1.69 μM [3]。

与对照组相比，腹腔注射2mg/kg多巴胺激动剂溴隐亭的组表现出显着的抗不动效果。当 7 天 MPE 治疗最后一次给药后 30 分钟给予溴隐亭并进行 FST 时，这种多巴胺能激动剂对 MPE（200 mg/kg，口服）的抗不动作用显示出显着且剂量-与单独 MPE 治疗相比，依赖性增强。与对照组相比，腹膜内 (ip) 2 mg/kg 多巴胺激动剂溴隐亭治疗组的不动时间显着缩短。当用 MPE 预处理 7 天后给予溴隐亭（100 和 200 mg/kg，po）时，与单独 MPE 治疗相比，MPE 的抗不动效果显着且呈剂量依赖性增强 [4]。当腹腔注射溴隐亭时，与假手术组相比，CCI-IoN 组的疼痛评分出现显着的剂量依赖性下降（0.1 mg 和 1 mg/Kg）。这种效果持续了六个小时。当应用最高剂量时，分数下降最多（P<0.01）。 DR1激动剂SKF8129用作阳性对照。腹膜内给药与假手术（盐水注射）相比，SMA 评分没有显着上升。当宫颈内给予溴隐亭时，SMA 评分比使用盐水注射作为假手术时低得多。溴隐亭的半衰期为 20 分钟。腹腔注射溴隐亭后，CCI-IoN α + α 6-OHDA 损伤组的 SMA 评分较假手术组显着下降，且呈剂量依赖性。撞击期间已经过去了六个小时。 SKF81297 的给药导致更高的异常性疼痛评分。与假手术（给大鼠注射生理盐水）相比，脑池内输注溴隐亭可显着降低 SMA 评分，且其效果持续 30 分钟[5]。

Absorption, Distribution and Excretion
Approximately 28% of the oral dose is absorbed; however, due to a significant first-pass effect, only 6% of the oral dose enters the systemic circulation unchanged. Bromocriptine and its metabolites appear in the blood within 10 minutes after oral administration and reach peak plasma concentrations within 1–1.5 hours. Serum prolactin levels may decrease within 2 hours after oral administration, reaching their maximum effect after 8 hours. In patients with acromegaly, a single oral dose of 2.5 mg results in a decrease in growth hormone concentrations within 1–2 hours, with the decreased concentration lasting at least 4–5 hours. The parent drug and its metabolites are almost entirely excreted by the liver, with only 6% excreted by the kidneys. Metabolism/Metabolites Completely metabolized in the liver, primarily through amide bond hydrolysis to produce lysergic acid and peptide fragments, both of which are inactive and non-toxic. Bromocriptine is metabolized by cytochrome P450 3A4 and is primarily excreted in feces via bile secretion.
The known human metabolites of bromocriptine include 5-bromo-N-[2,10-dihydroxy-7-(2-methylpropyl)-5,8-dioxo-4-propyl-2-yl-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecano-4-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolano[4,3-fg]quinoline-9-carboxamide and 5-bromo-N-[2,11-dihydroxy-7-(2-methylpropyl)-5,8-dioxo-4-propyl-2-yl-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecano-4-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolano[4,3-fg]quinoline-9-carboxamide. Bromocriptine is completely metabolized in the liver, primarily through amide bond hydrolysis to produce lysergic acid and peptide fragments, both of which are inactive and non-toxic. Bromocriptine is metabolized by cytochrome P450 3A4 and excreted mainly through bile in feces. Excretion pathway: The original drug and its metabolites are almost entirely excreted by the liver, with only 6% excreted by the kidneys. Half-life: 2-8 hours.

Toxicity Summary
The dopamine D2 receptor is a 7-transmembrane G protein-coupled receptor associated with Gi proteins. In lactating cells, activation of the dopamine D2 receptor leads to inhibition of adenylate cyclase, thereby reducing intracellular cAMP concentration and blocking the release of IP3-dependent Ca2+ from intracellular stores. The reduction in intracellular calcium levels may also be achieved through inhibition of calcium influx into voltage-gated calcium channels rather than inhibition of adenylate cyclase. Furthermore, receptor activation blocks phosphorylation of p42/p44 MAPK and reduces phosphorylation of MAPK/ERK kinases. MAPK inhibition appears to be mediated by c-Raf and β-Raf-dependent MAPK/ERK kinase inhibition. Dopamine-stimulated pituitary release of growth hormone is mediated by reduced intracellular calcium ion influx through voltage-gated calcium channels, rather than by inhibition of adenylate cyclase. Stimulation of dopamine D2 receptors in the substantia nigra-striatal pathway can improve muscle coordination in patients with movement disorders. Ergoline alkaloids have been shown to have significant affinity for serotonin receptors 5-HT1 and 5-HT2, dopamine D1 and D2, and α-adrenergic receptors. This can lead to a variety of effects, including vasoconstriction, seizures, and hallucinations. Bromocriptine exerts its effects by directly stimulating dopamine receptors in the striatum. (A2914, A2915, A2916, A2941)

[1]. Gardner B, et al. Agonist action at D2(long) dopamine receptors: ligand binding and functional assays. Br J Pharmacol. 1998 Jul;124(5):978-84.
[2]. Renodon A, et al. Bromocriptine is a strong inhibitor of brain nitric oxide synthase: possible consequences for the origin of its therapeutic effects.FEBS Lett. 1997 Apr 7;406(1-2):33-6.
[3]. Wynalda MA, et al. Assessment of potential interactions between dopamine receptor agonists and various human cytochrome P450 enzymes using a simple in vitro inhibition screen. Drug Metab Dispos. 1997 Oct;25(10):1211-4.
[4]. Rana DG, et al. Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression. Ayu. 2014 Jan;35(1):90-7.
[5]. Dieb W, et al. Nigrostriatal dopaminergic depletion increases static orofacial allodynia. J Headache Pain. 2016;17:11

Pharmacodynamics
Bromocriptine stimulates central dopaminergic receptors, thereby producing a variety of pharmacological effects. Currently, five dopamine receptors from two dopaminergic subfamilies have been identified. The dopamine D1 receptor subfamily includes D1 and D5 subreceptors, which are associated with motor disorders. The dopamine D2 receptor subfamily includes D2, D3, and D4 subreceptors, which are associated with the improvement of motor disorder symptoms. Therefore, specific agonist activity of D2 subfamily receptors (mainly D2 and D3 receptor subtypes) is a major target for dopaminergic anti-Parkinson's disease drugs. It is believed that postsynaptic D2 receptor activation is the main reason for the anti-Parkinson's disease effect of dopamine agonists, while presynaptic D2 receptor activation has a neuroprotective effect. This semi-synthetic ergot derivative exhibits potent agonist activity against dopamine D2 receptors. It also exhibits agonist activity against serotonin (5-HT)1D, dopamine D3, 5-HT1A, 5-HT2A, 5-HT1B, and 5-HT2C receptors (in descending order of binding affinity), antagonist activity against α2A-adrenergic receptors, α2C, α2B, and dopamine D1 receptors, partial agonist activity against 5-HT2B receptors, and inactivation of dopamine D4 and 5-HT7 receptors. Parkinson's disease is caused by the loss of approximately 80% dopaminergic activity in the substantia nigra-striatal pathway of the brain. Because the striatum is involved in regulating and coordinating the intensity of muscle activity (e.g., movement, balance, walking), loss of its activity can lead to dystonia (acute muscle contractions), Parkinson's syndrome (including symptoms such as bradykinesia, tremor, rigidity, and apathy), akathisia (restlessness), tardive dyskinesia (involuntary muscle movements usually associated with prolonged loss of dopaminergic activity), and neuroleptic malignancy, the latter occurring when dopamine is completely blocked in the substantia nigra-striatal pathway. Excessive dopaminergic activity in the mesolimbic pathway can lead to hallucinations and delusions; these side effects of dopamine agonists are common in patients with schizophrenia due to overactivity in this area of their brains. The hallucinogenic side effects of dopamine agonists may also be related to 5-HT2A receptor agonism. The tuberous-infundibular pathway originates in the hypothalamus and terminates in the pituitary gland. In this pathway, dopamine inhibits the secretion of prolactin from the anterior pituitary lactocytes. Increased dopaminergic activity in the tuberous infundibulum pathway can inhibit prolactin secretion; therefore, bromocriptine is an effective drug for treating diseases related to excessive prolactin secretion. Pulmonary fibrosis may be related to the agonistic effect of bromocriptine on 5-HT1B and 5-HT2B receptors.

C32H40BRN5O5

654.606

653.221

25614-03-3

Bromocriptine mesylate;22260-51-1

31101

Typically exists as solid at room temperature

1.52 g/cm3

891.3ºC at 760 mmHg

215-218

492.8ºC

4.15E-34mmHg at 25°C

1.696

3.397

118.21

3

6

5

43

1230

6

CC(C[C@H]1C(N2CCC[C@H]2[C@@]3(O)N1C([C@](NC([C@@H]4C=C5C6=C7C(C[C@H]5N(C4)C)=C(NC7=CC=C6)Br)=O)(O3)C(C)C)=O)=O)C

OZVBMTJYIDMWIL-AYFBDAFISA-N

InChI=1S/C32H40BrN5O5/c1-16(2)12-24-29(40)37-11-7-10-25(37)32(42)38(24)30(41)31(43-32,17(3)4)35-28(39)18-13-20-19-8-6-9-22-26(19)21(27(33)34-22)14-23(20)36(5)15-18/h6,8-9,13,16-18,23-25,34,42H,7,10-12,14-15H2,1-5H3,(H,35,39)/t18-,23-,24+,25+,31-,32+/m1/s1

Ergotaman-3',6',18-trione, 2-bromo-12'-hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl)-, (5'alpha)-

CB154 CB 154 Bromocriptine CB-154

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。