Synthetic Analogs of 6-Bromohypaphorine, a Natural Agonist of Nicotinic Acetylcholine Receptors, Reduce Cardiac Reperfusion Injury in a Rat Model of Myocardial Ischemia

• Published in: Doklady. Biochemistry and biophysics Vol. 503; no. 1; pp. 47 - 51
• Main Authors: Shaykhutdinova, E. R., Kondrakhina, A. E., Ivanov, I. A., Kudryavtsev, D. S., Dyachenko, I. A., Murashev, A. N., Tsetlin, V. I., Utkin, Yu. N.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.04.2022; Springer Nature B.V
• Subjects: Acetylcholine receptors (nicotinic); Agonists; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Coronary artery; Drug development; Heart attacks; Ischemia; Life Sciences; Molecular Biology; Myocardial infarction; Myocardial ischemia; Occlusion; Reperfusion; synthetic analogs; reperfusion injury; myocardial infarction; 6-bromohypaphorine; nicotinic acetylcholine receptor
• ISSN: 1607-6729; 1608-3091
• DOI: 10.1134/S1607672922020132

The data available to date indicate that the activation of nicotinic acetylcholine receptors (nAChR) of α7 type can reduce heart damage resulting from ischemia and subsequent reperfusion. We have studied two new synthetic D-analogs of 6-bromohypaphorine, which are selective agonists of α7 nAChR, in a rat model of myocardial ischemia. Acute myocardial infarction in animals was induced by occlusion of the left coronary artery with its subsequent reperfusion under mechanical lung ventilation. It was found that one of the analogs was more active, and treatment with it at the onset of reperfusion statistically reduced infarct size. This analog also prevented changes in the concentration of potassium and sodium ions in the blood, occurring during occlusion/reperfusion injury. The data obtained indicate that hypaphorine analogs are promising for the development of drugs that reduce the adverse effects of myocardial infarction.