Simkhovich B Z, Meĭrena D V, Shutenko Zh V, Khagi Kh B, Briede Ia L
Vopr Med Khim. 1988 Sep-Oct;34(5):30-4.
3-(2,2,2-trimethyl hydrazinium) propionate (THP) is known as an inhibitor of gamma-butyrobetaine hydroxylase in rat liver tissue. At the same time, THP, administered per os at a dose of 100 mg/kg within 10 days, prevented the isoproterenol-induced (subcutaneously, 50 mg/kg) acylcarnitine accumulation. This effect of THP, accompanied by a distinct decrease of free carnitine in rat myocardium, occurred due to inhibition of carnitine biosynthesis from gamma-butyrobetaine. THP protected the myocardium energetics against isoproterenol action as the drug prevented the acylcarnitine accumulation. Although D,L-carnitine (200 mg/kg, per os, 10 days) inhibited also the isoproterenol-stimulated acylcarnitine accumulation in rat myocardium and fatty acids of blood serum, in did not exhibit any favourable effect on myocardium bioenergetics. Inefficiency of D,L-carnitine as cardioprotective drug may be a result of intensification of fatty acids metabolism occurring simultaneously with isoproterenol-mediated myocardium ischemia. Use of inhibitors of carnitine-dependent oxidation of fatty acids oxidation (as exemplified by THP) in order to correct myocardium metabolism is of importance especially in relation to impairing effects caused by catecholamines.
3-(2,2,2-三甲基肼基)丙酸酯(THP)是大鼠肝脏组织中γ-丁酰甜菜碱羟化酶的一种抑制剂。同时,在10天内以100mg/kg的剂量经口给予THP,可预防异丙肾上腺素(皮下注射,50mg/kg)诱导的酰基肉碱蓄积。THP的这种作用伴随着大鼠心肌中游离肉碱的明显减少,这是由于抑制了γ-丁酰甜菜碱的肉碱生物合成所致。由于该药物预防了酰基肉碱的蓄积,THP保护心肌能量代谢免受异丙肾上腺素的影响。尽管D,L-肉碱(200mg/kg,经口,10天)也抑制了异丙肾上腺素刺激的大鼠心肌中酰基肉碱的蓄积以及血清脂肪酸的蓄积,但对心肌生物能量学未表现出任何有利影响。D,L-肉碱作为心脏保护药物无效可能是由于脂肪酸代谢增强与异丙肾上腺素介导的心肌缺血同时发生所致。使用肉碱依赖性脂肪酸氧化抑制剂(如THP)来纠正心肌代谢尤为重要,尤其是针对儿茶酚胺引起的损害作用。