Protective Role of Sarpogrelate in Combination with Bromocriptine and Cabergoline for Treatment of Diabetes in Alloxan-induced Diabetic Rats

BACKGROUND: Although dopamine D(2) 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(2)-like R agonists and the progress of myocardial injury, especially in the early phase of therapy. OBJECTIVE: 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(2) receptor agonists in a model of diabetic rats. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.