Noworyta-Sokołowska Karolina, Kamińska Katarzyna, Kreiner Grzegorz, Rogóż Zofia, Gołembiowska Krystyna
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna, 31-343, Kraków, Poland.
Department of Biochemistry, Polish Academy of Sciences, 12 Smętna, 31-343, Kraków, Poland.
Neurotox Res. 2016 Nov;30(4):606-619. doi: 10.1007/s12640-016-9654-0. Epub 2016 Jul 26.
5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT, 'foxy') is one of the most popular tryptamine hallucinogens in the illicit drug market. It produces serious adverse effects, but its pharmacological profile is not well recognized. In vitro data have shown that 5-MeO-DIPT acts as a potent serotonin transporter (SERT) inhibitor and displays high affinity at serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors. In this study, using microdialysis in freely moving rats, we examined the effect of 5-MeO-DIPT on dopamine (DA), serotonin (5-HT), and glutamate release in the rat striatum, nucleus accumbens, and frontal cortex. In search of a possible neurotoxic effect of 5-MeO-DIPT, we measured DA and 5-HT tissue content in the above rat brain regions and also determined the oxidative DNA damage with the comet assay. Moreover, we tested drug-elicited head-twitch response and a forepaw treading induced by 8-OH-DPAT. 5-MeO-DIPT at doses of 5, 10, and 20 mg/kg increased extracellular DA, 5-HT, and glutamate level but the differences in the potency were found between brain regions. 5-MeO-DIPT increased 5-HT and decreased 5-HIAA tissue content which seems to result from SERT inhibition. On the other hand, a decrease in DA, DOPAC, and HVA tissue contents suggests possible adaptive changes in DA turnover or damage of DA terminals by 5-MeO-DIPT. DNA single and double-strand breaks persisted up to 60 days after the treatment, indicating marked neurotoxicity of 5-MeO-DIPT. The induction of head-twitch response and potentiation of forepaw treading induced by 8-OH-DPAT indicate that hallucinogenic activity seems to be mediated through the stimulation of 5-HT2A and 5-HT1A receptors by 5-MeO-DIPT.
5-甲氧基-N,N-二异丙基色胺（5-MeO-DIPT，“狐仙”）是非法毒品市场上最受欢迎的色胺类致幻剂之一。它会产生严重的不良反应，但其药理学特性尚未得到充分认识。体外数据表明，5-MeO-DIPT是一种有效的血清素转运体（SERT）抑制剂，对血清素5-HT1A、5-HT2A和5-HT2C受体具有高亲和力。在本研究中，我们使用微透析技术对自由活动的大鼠进行实验，研究了5-MeO-DIPT对大鼠纹状体、伏隔核和额叶皮质中多巴胺（DA）、血清素（5-HT）和谷氨酸释放的影响。为了探究5-MeO-DIPT可能存在的神经毒性作用，我们测量了上述大鼠脑区中DA和5-HT的组织含量，并通过彗星试验测定了氧化性DNA损伤。此外，我们还测试了药物引发的头部抽搐反应以及由8-OH-DPAT诱导的前爪踏地反应。5-MeO-DIPT剂量为5、10和20mg/kg时可增加细胞外DA、5-HT和谷氨酸水平，但不同脑区之间的效力存在差异。5-MeO-DIPT增加了5-HT含量并降低了5-HIAA组织含量，这似乎是由于SERT抑制所致。另一方面，DA、DOPAC和HVA组织含量的降低表明5-MeO-DIPT可能导致DA代谢的适应性变化或DA终末损伤。治疗后DNA单链和双链断裂持续长达60天，表明5-MeO-DIPT具有明显的神经毒性。由5-MeO-DIPT诱导的头部抽搐反应和8-OH-DPAT诱导的前爪踏地反应增强表明，致幻活性似乎是通过5-MeO-DIPT对5-HT2A和5-HT1A受体的刺激介导的。
