Colao A, Lombardi G, Annunziato L
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Italy.
Expert Opin Pharmacother. 2000 Mar;1(3):555-74. doi: 10.1517/14656566.1.3.555.
Cabergoline (CAB) (1-[(6-allelylergolin-8 beta-yl)carbonyl]-1-[3-(dimethylamino)propyl]-3-ethyl-urea) is an ergoline derivative with potent, selective and long-lasting inhibitory activity on prolactin (PRL) secretion acting on dopamine receptors present in pituitary lactotrophes. Receptor binding studies have demonstrated that CAB has high in vitro selectivity and affinity for the subtype D2 of the dopamine receptor. In cultures of rat anterior pituitary cells, the concentrations of CAB and bromocriptine required to inhibit PRL secretory activity by 50% (IC50) were 0.1 and 3.4 nmol/l, respectively. As compared to bromocriptine, CAB was more potent in inhibiting the binding of [3H]N-n-propylnorapomorphine and it occupied the receptor for longer. These effects were observed in all areas of the rat brain. In vivo, CAB at doses of 0.125-1 mg twice weekly caused a dose-dependent suppression of PRL secretion in women with hyperprolactinaemia. CAB was shown to be significantly more effective than bromocriptine in inducing a complete biochemical response and clinical efficacy and was better tolerated than bromocriptine in the majority of patients. Notable tumour shrinkage until tumour disappearance was observed during CAB treatment in most patients with macroprolactinoma. CAB was also shown to be effective in patients resistant or poorly responsive to bromocriptine. In view of the limited data on CAB-associated pregnancies and the long half-life of the drug, it is currently recommended that women seeking to became pregnant, once ovulatory cycles have been established, should discontinue CAB therapy 1 month before they intend to conceive. However, no data on negative effects on pregnancy or offspring have been reported. The great efficacy of CAB together with its excellent tolerability makes this drug the current treatment of choice for the majority of patients with hyperprolactinaemic disorders. Very recently, the efficacy of CAB treatment has been reported in patients with acromegaly and clinically non-functioning adenomas with controversial results. CAB was also reported to have some efficacy in patients with Nelson's syndrome and Cushing's disease although these data are available only for limited case reports.
卡麦角林（CAB）（1-[(6-烯丙基麦角灵-8β-基)羰基]-1-[3-(二甲氨基)丙基]-3-乙基脲）是一种麦角灵衍生物，对垂体催乳细胞中存在的多巴胺受体具有强大、选择性和持久的抑制催乳素（PRL）分泌的活性。受体结合研究表明，CAB在体外对多巴胺受体的D2亚型具有高选择性和亲和力。在大鼠垂体前叶细胞培养中，抑制PRL分泌活性50%（IC50）所需的CAB和溴隐亭浓度分别为0.1和3.4 nmol/L。与溴隐亭相比，CAB在抑制[3H]N-正丙基去甲阿朴吗啡结合方面更有效，且其占据受体的时间更长。在大鼠脑的所有区域均观察到了这些效应。在体内，每周两次给予0.125 - 1 mg剂量的CAB可使高催乳素血症女性的PRL分泌呈剂量依赖性抑制。在诱导完全生化反应和临床疗效方面，CAB被证明比溴隐亭显著更有效，并且在大多数患者中比溴隐亭耐受性更好。在大多数大催乳素瘤患者的CAB治疗期间，观察到肿瘤明显缩小直至消失。CAB在对溴隐亭耐药或反应不佳的患者中也被证明有效。鉴于关于CAB相关妊娠的数据有限且该药物半衰期长，目前建议寻求怀孕的女性，一旦建立排卵周期，应在打算受孕前1个月停止CAB治疗。然而，尚未有关于对妊娠或后代产生负面影响的数据报道。CAB的高效性及其出色的耐受性使其成为大多数高催乳素血症疾病患者目前的首选治疗药物。最近，已有关于CAB治疗肢端肥大症和临床无功能腺瘤患者疗效的报道，但结果存在争议。也有报道称CAB对尼尔森综合征和库欣病患者有一定疗效，不过这些数据仅来自有限的病例报告。
