D2 receptor( Ki = 12.2 nM ); D3 receptor ( Ki = 12.2 nM ); D4 receptor ( Ki = 59.7 nM ); D1 receptor ( Ki = 1659 nM ); D5 receptor ( Ki = 1691 nM )

溴隐亭刺激 CHO 细胞中表达的 D2 多巴胺受体结合 [35S]-GTPγS，pEC50 为 8.15±0.05[1]。溴隐亭也是脑一氧化氮合酶的强抑制剂。麦角生物碱溴隐亭 (BKT) 被发现是纯化神经元一氧化氮合酶 (NOS) 的强抑制剂 (IC50=10±2 μM)，而它对诱导型巨噬细胞 NOS 的活性较差 (IC50>100 μM) [2] 。溴隐亭被发现可抑制至少一种人类细胞色素 P450 酶的活性。 Bromocriptine 是一种有效的 CYP3A4 抑制剂，计算出的相互作用 IC50 值为 1.69 μM[3]。

甲磺酸溴隐亭（2 mg/kg，腹膜内注射）在强迫游泳试验（FST）和悬尾试验（TST）的小鼠组中给药 7 天。与对照相比，溴隐亭组表现出显着的抗不动作用。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，与单独的 MPE 治疗相比，这种多巴胺能激动剂对 MPE（200 mg/kg，口服）的抗不动作用产生显着且剂量依赖性的增强。与对照组相比，溴隐亭治疗组的不动时间显着减少。与单独 MPE 治疗相比，用 MPE（100 和 200 mg/kg，口服）预处理 7 天后，溴隐亭给药显示出 MPE 抗不动作用的显着且剂量依赖性增强[4]。与假手术组（注射生理盐水的大鼠）相比，脑池内给予溴隐亭可显着降低静态机械异常性疼痛（SMA）评分，并且其效果持续30分钟。与假手术组相比，腹腔内给予溴隐亭可导致 CCI-IoN 组疼痛评分显着、剂量依赖性（0.1 mg 和 1 mg/kg）下降，其效果持续 6 小时。最高剂量引起最高的评分下降（P<0.01）。溴隐亭作用持续20分钟。与假手术组相比，腹膜内给予溴隐亭会导致 CCI-IoN+6-OHDA 损伤组中 SMA 评分出现显着的剂量依赖性下降。其作用持续6小时[5]。

进行[35S]-GTPγS结合测定。 30°C 下，细胞膜 (25 ±75 ug) 在缓冲液 B 中孵育 30 分钟，缓冲液 B 含有 0.1 mM 二硫苏糖醇 (DTT)、1 uM GDP 和 0.9 mL 体积的药物。这种预孵育保证了当添加最终浓度的 [35S]-GTPγS (50±150 pM)（在 100 uL 缓冲液 B 中）开始反应时，测试的激动剂处于平衡状态。除非另有说明，否则将测定混合物再孵育 20 分钟。快速过滤结束测定，并如前面提到的放射性配体结合测定那样测量结合的放射性。总共不到 20% 的添加 GTPγS 与 [35S]-GTPγS 结合[1]。

Mice: There are 150 total Swiss mice (20–25 g) of either sex used. One such agonist for the dopamine receptor (D2) is bromocriptine mesylate. Distilled water is used to dilute the medication haloperidol, which is then injected. A single drop of glacial acetic acid is used to dissolve bromocriptine mesylate, which is then diluted with distilled water to the desired volume. Imipramine dissolves in 0.9% regular saline. In groups of mice undergoing the Forced Swimming Test (FST) and Tail Suspension Test (TST), haloperidol (0.1 mg/kg, i.p.) and bromocriptine mesylate (2 mg/kg, i.p.) are given for 7 days. As a standard, positive control groups receive imipramine (10 mg/kg, p.o.) for seven days.
Rats: The rats used are adult male Sprague-Dawleys (N=112, 275–325 g). A couple of weeks following the 6-OHDA injection, the animals undergo a brief (less than three minutes) mask-applied 2% halothane anesthesia before receiving either the vehicle (5 μL of 0.9% saline) or bromocriptine (7 μg/kg dissolved in 5 μL vehicle) intraperitoneally. We used concentrations of SKF81297 (3 mg/kg dissolved in 0.9% saline) and bromocriptine (1 mg/kg) for intraperitoneal injection. A blind experimenter places the rats in the observation field for a 40-minute period test after they have recovered for less than two minutes.

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]. Agonist action at D2(long) dopamine receptors: ligand binding and functional assays. Br J Pharmacol. 1998 Jul;124(5):978-84.

[2]. 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]. 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]. Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression. Ayu. 2014 Jan;35(1):90-7.

[5]. 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.

C33H44BRN5O8S

750.700160000001

749.209

C, 52.80; H, 5.91; Br, 10.64; N, 9.33; O, 17.05; S, 4.27

22260-51-1

Bromocriptine; 25614-03-3

31101

White to off-white solid powder

891.3ºC at 760 mmHg

215-218

492.8ºC

0mmHg at 25°C

3.982

180.96

3

6

5

43

1230

6

[H][C@@]12CC3=C(Br)NC4=CC=CC(C1=C[C@@H](C(N[C@@]5(C(C)C)C(N6[C@@H](CC(C)C)C(N7CCC[C@]7([C@]6(O)O5)[H])=O)=O)=O)CN2C)=C43.OS(=O)(C)=O

NOJMTMIRQRDZMT-GSPXQYRGSA-N

InChI=1S/C32H40BrN5O5.CH4O3S/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;1-5(2,3)4/h6,8-9,13,16-18,23-25,34,42H,7,10-12,14-15H2,1-5H3,(H,35,39);1H3,(H,2,3,4)/t18-,23-,24+,25+,31-,32+;/m1./s1

(6aR,9R)-5-bromo-N-[(1S,2S,4R,7S)-2-hydroxy-7-(2-methylpropyl)-5,8-dioxo-4-propan-2-yl-3-oxa-6,9-diazatricyclo[7.3.0.02,6]dodecan-4-yl]-7-methyl-6,6a,8,9-tetrahydro-4H-indolo[4,3-fg]quinoline-9-carboxamide;methanesulfonic acid

CB154; CB-154; CB 154; Bromocriptine Mesylate; 2-Bromoergocryptine Mesylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮和光照。

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

DMSO: ~100~250 mg/mL (133.2~333.0 mM)
H2O: ~1.1 mg/mL (~1.5 mM)

配方 1 中的溶解度: ≥ 2.08 mg/mL (2.77 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 20.8 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: ≥ 2.08 mg/mL (2.77 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 20.8 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: ≥ 2.08 mg/mL (2.77 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 20.8 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

---

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。