Background
IC50: 0.1 nM
Unlike other pituitary hormones, prolactin (PRL) secretion is predominantly inhibited by dopamine secreted by the hypothalamus. Cabergoline is an ergoline derivative with potent, selective and long-lasting inhibitory activity on PRL secretion acting on dopamine receptors present in pituitary lactotrophes.
In vitro: Receptor binding studies have demonstrated that cabergoline has high in vitro selectivity and affinity for the subtype D2 of the dopamine receptor. In rat anterior pituitary cells, the concentration of cabergoline required to inhibit PRL secretory activity by 50% were 0.1 nmol/l [1].
In vivo: In various animal models, cabergoline markedly reduced plasma PRL levels in vivo after single or multiple doses, and the PRL-lowering effects appeared 2 - 8 h after administration lasting for 72 h or longer. In addition, a single dose of cabergoline 0.6 mg/kg to rats, inhibited the serum levels of PRL for 6 days significantly [1].
Clinical trial: Cabergoline at doses of 0.125 - 1 mg twice a week caused a dose-dependent suppression of PRL secretion in women with hyperprolactinaemia. cabergoline was shown to be more effective than bromocriptine in inducing a complete biochemical response and clinical efficacy and was better tolerated than bromocriptine in the majority of patients [1].
Reference:
[1] Annamaria Colao, Gaetano Lombardi & Lucio Annunziato.? Cabergoline. Exp. Opin. Pharmacother. (2000) 1(3):555-574
Protocol
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Cell experiment:
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Primary cortical neurons are prepared. Cabergoline (10 μM; except for experiments of dose-dependency) is applied to cortical cells at DIV 6-7. After 24-hour Cabergoline treatment (except for examination of pretreatment time-dependency of Cabergoline), H2O2 (50 μM; except for the dose-dependency of H2O2) is added. All inhibitors and antagonists, including spiperone, U0126, SB203580, SP600125, AP5, and nifedipine are applied 20 min before Cabergoline or H2O2 addition. L-glutamate is added at DIV 7-8 for cell death induction. Cell survival rate is measured by MTT assay. After the indicated treatment with drugs is completed, culture medium is replaced with 200 μL fresh medium containing 40 μl MTT solution (2.5 mg/mL, diluted in PBS) and cells are incubated at 37°C for 1.5-2.5 hours. Then, 200 μL lysis buffer containing isopropyl alcohol is applied to each well and mixed by pipetting. Each sample is moved to a 96-well plate and its absorbance at 570 nm is measured using an iMark Micro plate leader. Cell survival rate is quantitated by absorbance measurement, because MTT (yellow) is deoxidized to formazan (violet) in proportion to mitochondrial activity[1].
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Animal experiment:
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Mice[2] Female and male C57BL/6J mice are used.Cabergoline is dissolved in 100% pharmasolve and then diluted with 20% β-cyclodextrin in water to yield a final concentration of 0.15-0.5 mg/mL Cabergoline. Mice received a 0.3-mg/kg ip injection of Cabergoline or vehicle. All drugs are prepared within 48 hours of experiment and stored at 4°C. Solutions are allowed to reach at room temperature before injection.
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参考文献:
[1]. Odaka H, et al. Cabergoline, dopamine D2 receptor agonist, prevents neuronal cell death under oxidative stress via reducing excitotoxicity. PLoS One. 2014 Jun 10;9(6):e99271.
[2]. Jefferson F, et al. A dopamine receptor d2-type agonist attenuates the ability of stress to alter sleep in mice. Endocrinology. 2014 Nov;155(11):4411-21.
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