Effects of rotigotine and rotigotine extended-release microsphere therapy on myocardial ischemic injury in mice.

Abstract

Rotigotine is a dopamine receptor agonist that can improve motor function in Parkinson's disease (PD) patients. Rotigotine extended-release microsphere (RoMS) is an extended-release intramuscular formulation that exhibits a sustained release of rotigotine over a 14-day period. The clinical trials of RoMS has been carried out in USA and China. The purpose of this study is to observe the effects of RoMS therapy on myocardial ischemic injury in mice, to know whether RoMS alleviate or deteriorate the myocardial ischemic injury while PD patient has onset of myocardial ischemia concurrent after administered with RoMS. A mouse model of myocardial ischemia was established using isoproterenol, and mice were pretreated with rotigotine or RoMS before inducing myocardial ischemic injury. The effects of rotigotine or RoMS therapy on the degree of myocardial ischemic injury were studied by evaluating troponin I level, creatine kinase-MB (CK-MB) activity, and histopathological changes in cardiomyocytes. The dopamine receptor blocker chlorpromazine was used to further investigate the effects of rotigotine or RoMS on myocardial ischemic injury. Furthermore, serum rotigotine concentrations were also assayed. When myocardial ischemia occurred during rotigotine or RoMS administration, troponin I level and CK-MB activity were decreased, and ischemia-induced histopathological changes in cardiomyocytes were alleviated. The effects of rotigotine were maintained only 12 h and after that no protective effect was observed. RoMS releases continuously into the circulation after intramuscular injection. The cardioprotective effects of RoMS were maintained 14 days after a single RoMS administration. When combined with chlorpromazine, the protective effects of rotigotine on myocardial ischemic injury were eliminated, and the protective effects of RoMS were also partially abolished. In the animal model of myocardial ischemia, pretreatment with rotigotine or RoMS does not deteriorate, but can alleviate cardiomyocyte injury. Furthermore, RoMS pretreatment show long-term and continuous protective effects on cardiomyocyte injury. RoMS therapy in PD patients at high risk for cardiovascular diseases may attenuate the degree of cardiomyocyte injury caused by ischemia.

• Authors: Huaiyou Lv, Fei Yu, Chunjie Sha, Yanan Huang, Yongying Lu, Leiming Zhang, Rong Zhai, Tian Wang, Fenghua Fu
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 134 Pg. 1-6 (Jun 15 2019) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 30959104 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Cardiotonic Agents
• Dopamine Agonists
• Tetrahydronaphthalenes
• Thiophenes
• Troponin I
• rotigotine
• Creatine Kinase, MB Form
• Isoproterenol
• Chlorpromazine

Topics

• Animals
• Cardiotonic Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Chlorpromazine (antagonists & inhibitors)
• Creatine Kinase, MB Form (drug effects, metabolism)
• Dopamine Agonists (administration & dosage, pharmacokinetics, therapeutic use)
• Isoproterenol (pharmacology)
• Male
• Mice
• Microspheres
• Models, Animal
• Myocardial Ischemia (drug therapy)
• Myocytes, Cardiac (drug effects, pathology)
• Parkinson Disease (drug therapy)
• Tetrahydronaphthalenes (administration & dosage, pharmacokinetics, therapeutic use)
• Thiophenes (administration & dosage, pharmacokinetics, therapeutic use)
• Troponin I (drug effects, metabolism)