Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital and University of Basel, CH-4031 Basel, Switzerland.
J Clin Endocrinol Metab. 2011 Sep;96(9):2844-50. doi: 10.1210/jc.2011-1143. Epub 2011 Jun 29.
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) misuse is associated with hyponatremia particularly in women. Hyponatremia is possibly due to inappropriate secretion of plasma arginine vasopressin (AVP).
To assess whether MDMA increases plasma AVP and copeptin in healthy male and female subjects and whether effects depend on MDMA-induced release of serotonin and norepinephrine. Copeptin, the C-terminal part of the AVP precursor preprovasopressin, is cosecreted with AVP and can be determined more reliably.
We used a randomized placebo-controlled crossover design. Plasma and urine osmolalities as well as AVP and copeptin levels were measured in 16 healthy subjects (eight female, eight male) at baseline and after MDMA (125 mg) administration. In addition, we tested whether effects of MDMA on AVP and copeptin secretion can be prevented by pretreatment with the serotonin and norepinephrine transporter inhibitor duloxetine (120 mg), which blocks MDMA-induced transporter-mediated release of serotonin and norepinephrine.
MDMA significantly elevated plasma copeptin levels at 60 min and at 120 min compared with placebo in women but not in men. The copeptin response to MDMA in women was prevented by duloxetine. MDMA also nonsignificantly increased plasma AVP levels in women, and the effect was prevented by duloxetine. Although subjects drank more water after MDMA compared with placebo administration, MDMA tended to increase urine sodium levels and urine osmolality compared with placebo, indicating increased renal water retention.
MDMA increased plasma copeptin, a marker for AVP secretion, in women but not in men. This sex difference in MDMA-induced AVP secretion may explain why hyponatremia is typically reported in female ecstasy users. The copeptin response to MDMA is likely mediated via MDMA-induced release of serotonin and/or norepinephrine because it was prevented by duloxetine, which blocks the interaction of MDMA with the serotonergic and noradrenergic system.
3,4-亚甲基二氧甲基苯丙胺（MDMA，摇头丸）滥用与低钠血症有关，尤其是在女性中。低钠血症可能是由于血浆精氨酸加压素（AVP）分泌不当所致。
评估 MDMA 是否会增加健康男性和女性受试者的血浆 AVP 和 copeptin，以及这些效应是否取决于 MDMA 诱导的 5-羟色胺和去甲肾上腺素的释放。Copeptin 是 AVP 前体前脑啡肽的 C 端部分，与 AVP 一起被共同分泌，并且可以更可靠地测定。
我们使用随机安慰剂对照交叉设计。在基线和 MDMA（125mg）给药后，测量了 16 名健康受试者（8 名女性，8 名男性）的血浆和尿液渗透压以及 AVP 和 copeptin 水平。此外，我们还测试了 5-羟色胺和去甲肾上腺素转运体抑制剂度洛西汀（120mg）预处理是否可以预防 MDMA 对 AVP 和 copeptin 分泌的作用，度洛西汀可以阻断 MDMA 诱导的转运体介导的 5-羟色胺和去甲肾上腺素释放。
与安慰剂相比，MDMA 在 60 分钟和 120 分钟时显著升高了女性的血浆 copeptin 水平，但在男性中没有。度洛西汀可预防女性对 MDMA 的 copeptin 反应。MDMA 还轻微增加了女性的血浆 AVP 水平，并且该作用也被度洛西汀所预防。尽管与安慰剂相比，MDMA 给药后受试者饮用了更多的水，但与安慰剂相比，MDMA 倾向于增加尿钠水平和尿渗透压，这表明肾水潴留增加。
MDMA 增加了女性血浆 copeptin，这是 AVP 分泌的标志物，但在男性中没有。这种 MDMA 诱导的 AVP 分泌的性别差异可能解释了为什么低钠血症通常在女性摇头丸使用者中报告。Copeptin 对 MDMA 的反应可能是通过 MDMA 诱导的 5-羟色胺和/或去甲肾上腺素释放介导的，因为它被度洛西汀阻断了 MDMA 与 5-羟色胺能和去甲肾上腺素能系统的相互作用。
