Institute for Pharmacology and Toxicology, Medical Faculty, Martin Luther University Halle-Wittenberg, 06097 Halle, Germany.
Department of Cardiac Surgery, Mid-German Heart Center, University Hospital Halle, 06097 Halle, Germany.
Int J Mol Sci. 2024 Aug 15;25(16):8887. doi: 10.3390/ijms25168887.
The present study examined three hallucinogenic amphetamine derivatives, namely, 2,5-dimethoxy-4-iodoamphetamine (DOI) as well as 2,5-dimethoxy-4-methylamphetamine (DOM) and 4-methylmethcathinone (mephedrone). The objective of this study was to test the hypothesis that DOI, DOM, and mephedrone would increase the contractile force in isolated human atrial preparations in a manner similar to amphetamine. To this end, we measured contractile force under isometric conditions in electrically stimulated (1 Hz) human atrial preparations obtained during open surgery. DOI and DOM alone or in the presence of isoprenaline reduced the contractile force concentration-dependently in human atrial preparations. These negative inotropic effects of DOM and DOI were not attenuated by 10 µM atropine. However, mephedrone increased the contractile force in human atrial preparations in a concentration- and time-dependent manner. Furthermore, these effects were attenuated by the subsequent addition of 10 µM propranolol or pretreatment with 10 µM cocaine in the organ bath. Therefore, it can be concluded that amphetamine derivatives may exert opposing effects on cardiac contractile force. The precise mechanism by which DOI and DOM exert their negative inotropic effects remains unknown at present. The cardiac effects of mephedrone are probably due to the release of cardiac noradrenaline.
本研究检测了三种致幻性苯丙胺衍生物，即 2,5-二甲氧基-4-碘苯丙胺（DOI）以及 2,5-二甲氧基-4-甲基苯丙胺（DOM）和 4-甲基甲卡西酮（mephedrone）。本研究旨在验证以下假设，即 DOI、DOM 和 mephedrone 会以类似于安非他命的方式增加人心房组织的收缩力。为此，我们在开放性手术中获取的人心房组织上进行电刺激（1 Hz）的等长条件下测量收缩力。DOI 和 DOM 单独或与异丙肾上腺素同时存在时，以浓度依赖性方式减少人心房组织的收缩力。DOM 和 DOI 的这种负性肌力作用不受 10 µM 阿托品的减弱。然而，mephedrone 以浓度和时间依赖性方式增加人心房组织的收缩力。此外，这些作用可被随后在器官浴中加入 10 µM 普萘洛尔或预先用 10 µM 可卡因预处理所减弱。因此，可以得出结论，安非他命衍生物可能对心脏收缩力产生相反的作用。目前，DOI 和 DOM 发挥负性肌力作用的确切机制尚不清楚。mephedrone 的心脏效应可能归因于心脏去甲肾上腺素的释放。
