Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Daru. 2013 Jan 17;21(1):9. doi: 10.1186/2008-2231-21-9.
Ecstasy is one of the popular illicit drugs in the world and its usage has been recently increased in Iran. This compound can destroy the serotonergic neurons and produces cognitive and psychopathology diseases. 3,4-dihydroxymethamphetamine (HHMA) which is the main metabolite of this compound, seems to be responsible for this effect. However, no consensus has been reached among the researchers about its role. This disagreement between the researches may be due to failure in determination of HHMA as free form in physiological fluids. In this study, the stability of this crucial metabolite of ecstasy was examined in different mediums.
The stability of HHMA was studied in the perfusion medium and water at 100 and 10 ng/mL concentrations. Moreover, the effect of temperature (0-25°C), pH (3-10), calcium chloride (0-150 g/L) and ethylenediaminetetraacetic acid (EDTA) on the stability of HHMA was also examined.
Our result suggested that the free form of HHMA could be degraded in the perfusion medium. The rate of this degradation has direct proportion to temperature (at 25°C = 0.037 min-1 and at 0°C = 0.002 min-1). Calcium chloride and sodium bicarbonate are two responsible components in this instability. Moreover, the alkaline pHs and increasing the shaking time can accelerate this effect. Although, while degradation was prevented at pH=3, EDTA could only reduce this rate about 30%.
Calcium cation can act as an accelerator of HHMA degradation. Therefore, the perfusion medium should not contain Ca2+ and the pH of medium is better to be adjusted at acidic range. Since, the internal cellular source of calcium is endoplasmic reticulum system, it can be assumed that, this cation may change HHMA and dopamine to reactive compounds that can bind covalently to the cysteinyl group of biological compounds and damage cellular components.
摇头丸是世界上流行的非法药物之一，最近在伊朗的使用有所增加。这种化合物会破坏 5-羟色胺能神经元，并导致认知和精神病理学疾病。3,4-二羟基甲安非他命（HHMA）是这种化合物的主要代谢物，似乎是造成这种影响的原因。然而，研究人员对此并没有达成共识。研究人员之间的这种分歧可能是由于未能确定生理液体中的 HHMA 是游离形式。在这项研究中，研究了不同介质中摇头丸这种关键代谢物的稳定性。
研究了 HHMA 在灌注介质中和 100 和 10ng/mL 浓度的水中的稳定性。此外，还研究了温度（0-25°C）、pH 值（3-10）、氯化钙（0-150g/L）和乙二胺四乙酸（EDTA）对 HHMA 稳定性的影响。
我们的结果表明，HHMA 的游离形式可在灌注介质中降解。这种降解的速率与温度呈直接比例（在 25°C 时为 0.037 min-1，在 0°C 时为 0.002 min-1）。氯化钙和碳酸氢钠是这种不稳定性的两个责任成分。此外，碱性 pH 值和增加振摇时间可以加速这种效应。虽然在 pH=3 时可以防止降解，但 EDTA 只能将这种速率降低约 30%。
钙离子可以作为 HHMA 降解的加速剂。因此，灌注介质中不应含有 Ca2+，并且介质的 pH 值最好调节为酸性范围。由于细胞内钙的来源是内质网系统，可以假设这种阳离子可能会使 HHMA 和多巴胺变成反应性化合物，与生物化合物的半胱氨酸基团共价结合，从而破坏细胞成分。
