Fouad Shalaby Mohammed, Latif Hekma A Abd El, Yamani Mohamed El, Galal May Ahmed, Kamal Sherifa, Sindi Ikhlas
Pharmaceutical Sciences Department, Pharmacy Programme, Batterjee Medical College, Jeddah, Kingdom of Saudi Arabia.
Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Curr Ther Res Clin Exp. 2021 Oct 12;95:100647. doi: 10.1016/j.curtheres.2021.100647. eCollection 2021.
Although dopamine D receptor agonists, bromocriptine and cabergoline, are notable medications in the treatment of Parkinsonism, hyperprolactinemia, and hyperglycemia, there is an identified relationship between the utilization of D-like R agonists and the progress of myocardial injury, especially in the early phase of therapy.
This investigation aimed to examine the potential activity of sarpogrelate (a 5-hydroxytryptamine 2A [5-HT2A] receptor blocker) in reducing myocardial injury prompted by extended haul utilization of D receptor agonists in a model of diabetic rats.
In the in vivo studies, both bromocriptine and cabergoline were managed independently and combined with sarpogrelate for about a month in diabetic nephropathy rats. Blood glucose level and other myocardial biochemical parameters were estimated. The probable mechanism for insulin secretagogue action was evaluated through in vitro isolated islets study. Sodium/potassium-adenosine triphosphatase activity was assayed in an isolated microsomal fraction of the renal cortex. Isolated perfused rat hearts were treated with different doses of dopamine before and after being subjected to the tested drugs, dose response of heart rate, and heart contractility were recorded.
Bromocriptine and cabergoline created a significant reduction in blood glucose level without any action on insulin secretagogues. Bromocriptine prevented the loss of sodium/potassium-adenosine triphosphatase activity in the cortex of an ischemic kidney. Treatment of bromocriptine or cabergoline with sarpogrelate altogether decreased the levels of the elevated myocardial biomarkers in serum. Administration of different doses of dopamine in presence of bromocriptine or capergoline resulted in significantly rising in the heart rate percentage comparing to dopamine alone. A mix of bromocriptine or cabergoline with sarpogrelate diminished both heart rate and contractility, respectively.
The examination demonstrated that the combined use of sarpogrelate with bromocriptine or cabergoline decreased the potential adverse effects of these 2 drugs on myocardial tissues.
尽管多巴胺D受体激动剂溴隐亭和卡麦角林是治疗帕金森症、高泌乳素血症和高血糖的重要药物，但已确定D样受体激动剂的使用与心肌损伤进展之间存在关联，尤其是在治疗早期。
本研究旨在探讨在糖尿病大鼠模型中，沙格雷酯（一种5-羟色胺2A[5-HT2A]受体阻滞剂）对长期使用D受体激动剂所致心肌损伤的潜在保护作用。
在体内研究中，将溴隐亭和卡麦角林分别单独给药，并与沙格雷酯联合应用于糖尿病肾病大鼠约1个月。检测血糖水平及其他心肌生化指标。通过体外分离胰岛实验评估胰岛素促分泌作用的可能机制。在肾皮质分离的微粒体部分测定钠/钾-三磷酸腺苷酶活性。在给予受试药物前后，用不同剂量的多巴胺处理离体灌注大鼠心脏，记录心率和心脏收缩力的剂量反应。
溴隐亭和卡麦角林可显著降低血糖水平，但对胰岛素促分泌剂无作用。溴隐亭可防止缺血性肾皮质中钠/钾-三磷酸腺苷酶活性的丧失。溴隐亭或卡麦角林与沙格雷酯联合治疗可共同降低血清中升高的心肌生物标志物水平。与单独使用多巴胺相比，在溴隐亭或卡麦角林存在的情况下给予不同剂量的多巴胺可导致心率百分比显著升高。溴隐亭或卡麦角林与沙格雷酯的组合分别降低了心率和收缩力。
研究表明，沙格雷酯与溴隐亭或卡麦角林联合使用可降低这两种药物对心肌组织的潜在不良反应。
