1、Product Data SheetBromocriptine mesylateCat. No.: HY-12705ACAS No.: 22260-51-1分式: CHBrNOS分量: 750.7作靶點: Dopamine Receptor; Autophagy作通路: GPCR/G Protein; Neuronal Signaling; Autophagy儲存式: 4C, sealed storage, away from moisture and light* In solvent : -80C, 6 months; -20C, 1 month (sealed storage, away

2、 frommoisture and light)溶解性數(shù)據(jù)體外實驗 DMSO : 75 mg/mL (99.91 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 1.3321 mL 6.6605 mL 13.3209 mL5 mM 0.2664 mL 1.3321 mL 2.6642 mL10 mM 0.1332 mL 0.6660 mL 1.3321 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 mo

3、nths; -20C, 1 month (sealed storage, away from moisture and light)。-80C儲存時，請在 6 個內(nèi)使，-20C 儲存時，請在 1 個內(nèi)使。體內(nèi)實驗請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都請先按?In Vitro 式配制澄清的儲備液，再依次添加助溶劑：為保證實驗結(jié)果的可靠性，澄 的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的式助溶1. 請依序添加每種溶劑： 10% DMSO

4、 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (3.33 mM); Clear solution此案可獲得 2.5 mg/mL (3.33 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/

5、mL (3.33 mM); Suspended solution; Need ultrasonic此案可獲得 2.5 mg/mL (3.33 mM) 的均勻懸濁液，懸濁液可于服和腹腔注射。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合Page 1 of 2 www.MedChemE均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (3.33 mM); Clear solution此案可獲得 2.5 mg/mL (3.33 mM，

6、飽和度未知) 的澄 溶液，此案不適于實驗周 期在半個以上的實驗。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Bromocriptine mesylate種有效的多巴胺 D2/D3 受體激動劑，結(jié)合多巴胺 D2 受體，pKi 為 8.050.2。IC & Target pKi: 8.050.2 (dopamine D2 receptor)1體外研究 Bromocriptine stimulates 35S-GTPS binding at D2 dopamine receptor

7、 expressed in CHO cells with pEC50 of8.150.051. Bromocriptine also is a strong inhibitor of brain nitric oxide synthase. The ergot alkaloid Bromocriptine(BKT) is found to act as a strong inhibitor of purified neuronal nitric oxide synthase (NOS) (IC50=102 M) whereas itis poorly active towards induci

8、ble macrophage NOS (IC50100 M) 2. Bromocriptine is found to inhibit the activity ofat least one human cytochrome P450 enzyme. Bromocriptine is a potent inhibitor of CYP3A4 with a calculated IC50value for the interaction of 1.69 M3.體內(nèi)研究 Bromocriptine mesylate (2 mg/kg, i.p.) is administered for 7 day

9、s in groups of mice in forced swimming test (FST) andtail suspension test (TST). Bromocriptine group shows significant anti-immobility action as compared to control.When Bromocriptine administered 30 min after the last dose of 7 days MPE treatment and subjected to FST, thisdopaminergic agonist produ

10、ces significant and dose dependent potentiation of anti-immobility action of MPE (200mg/kg, p.o.) as compared to MPE treatment alone. Bromocriptine treatment group shows a significant reduction ofimmobility time as compared to control. Bromocriptine administration after 7 days pretreatment with MPE

11、(100 and200 mg/kg, p.o.) shows significant and dose dependent potentiation of anti-immobility action of MPE as compared toMPE treatment alone4. Intracisternal administration of Bromocriptine decreases significantly the static mechanicalallodynia (SMA) score compared to that of sham (saline-injected

12、rats) and its effect lasted for 30 min. Intraperitonealadministration of Bromocriptine induces a significant, dose dependent (0.1 mg and 1 mg/kg) decrease in pain scoresin CCI-IoN group when compared to sham and its effect lasted for 6 h. The highest dose induces the highest scoredecrease (P0.01). B

13、romocriptine effect lasts for 20 min. Intraperitoneal administration of Bromocriptine induces asignificant dose dependent decrease in SMA score in CCI-IoN+6-OHDA lesioned group compared to that of sham. Itseffect lasts for 6 h5.PROTOCOLKinase Assay 1 The 35S-GTPS binding assay is carried out. Cell m

14、embranes (25 75 ug) are incubated in Buffer B containing 0.1mM dithiothreitol (DTT) and 1 uM GDP and drugs in a volume of 0.9 mL for 30 min at 30C. This preincubationensures that the agonists tested are at equilibrium when the 35S-GTPS (50150 pM, final concentration) is added(in 100 uL ofBuffer B) t

15、o initiate the reaction. The assay mixture is incubated for a further 20 min unless otherwisestated. The assays are terminated by rapid filtration and bound radio-activity determined as described for the radio-ligand binding assays above. The total binding of 35S-GTPS is less than 20% of that added1

16、.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice4Administration 45 Swiss mice (20-25 g) of either sex (total 150) are used. Bromocriptine mesylate is used as dopamine receptor (D2)agonist. Haloperidol is diluted in distilled water which is u

17、sed for a vehicle of injection. Bromocriptine mesylate isPage 2 of 3 www.MedChemEdissolved in one drop of glacial acetic acid and made up to volume in distilled water. Imipramine is dissolved in 0.9%normal saline. Haloperidol (0.1 mg/kg, i.p.) and Bromocriptine mesylate (2 mg/kg, i.p.) are administe

18、red for 7 days ingroups of mice in Forced Swimming Test (FST) and Tail Suspension Test (TST). Imipramine (10 mg/kg, p.o.) as astandard is administered in positive control groups for 7 days.Rats5Adult male Sprague-Dawley rats (N=112, 275-325 g) are used. Two weeks after the 6-OHDA injection, the anim

19、als arebriefly (3 min) anesthetized with 2 % halothane using a mask and received for intracisternal administrationBromocriptine (7 g/kg dissolved in 5 L vehicle) or the vehicle alone (5 L of 0.9 % saline). For i.p. injection we usedBromocriptine (1 mg/kg) and SKF81297 (3 mg/kg dissolved in 0.9 % sal

20、ine) concentrations. Following a recoveryperiod (2 min), the rats are placed in the observation field for 40 min period-test by a blind-experimenter.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Nat Commun. 2020 Feb 18;11(1):941.See more c

21、ustomer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. 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.FEBSLett. 1997 Apr 7;406(1-2):33-6.3. Wynalda MA, e