Botanas Chrislean Jun, de la Peña June Bryan, Dela Peña Irene Joy, Tampus Reinholdgher, Yoon Robin, Kim Hee Jin, Lee Yong Sup, Jang Choon Gon, Cheong Jae Hoon
Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815 Nowon-gu, Seoul 139-742, South Korea.
Laboratory of Medicinal Chemistry, School of Pharmacy, Kyunghee University, Seoul 130-701, South Korea.
Pharmacol Biochem Behav. 2015 Jun;133:31-6. doi: 10.1016/j.pbb.2015.03.007. Epub 2015 Mar 17.
Methoxetamine (MXE) is an N-methyl-d-aspartate (NMDA) receptor antagonist that is chemically and pharmacologically similar to ketamine. Recently, there have been many reports regarding its use/misuse in humans which have resulted in serious or even fatal outcomes. Despite these reports, MXE is not controlled or regulated in many countries which may be partly due to the lack of scientific evidence regarding its abuse potential. Thus, in the present study we evaluated the abuse potential (rewarding and reinforcing effects) of MXE through the conditioned place preference (CPP) and self-administration (SA) tests in Sprague-Dawley rats. In addition, locomotor activity during the conditioning phase of the CPP was also analyzed. Ketamine was used as a reference drug. MXE (2.5 and 5mg/kg) induced significant CPP in rats, an effect comparable to that of ketamine (5mg/kg). Interestingly, MXE did not produce any locomotor alterations while ketamine decreased the locomotor activity of rats. In the SA test, rats showed modest self-administration of MXE (0.25, 0.5, 1.0mg/kg/infusion), while ketamine (0.5mg/kg/infusion) was robustly self-administered. These results demonstrate that MXE, similar to ketamine, has rewarding and reinforcing effects in rats. The present study strongly suggests that MXE has a potential for human abuse. In addition, the discrepant effects of MXE and ketamine on locomotor activity and rate of self-administration propose that the psychopharmacological effects of these drugs may diverge in some aspects. More importantly, this study advocates the careful monitoring and prompt regulation of MXE and its related substances.
甲氧基氯胺酮（MXE）是一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，在化学和药理上与氯胺酮相似。最近，有许多关于其在人类中使用/滥用的报道，这些报道导致了严重甚至致命的后果。尽管有这些报道，但MXE在许多国家并未受到管控，这可能部分归因于缺乏关于其滥用潜力的科学证据。因此，在本研究中，我们通过条件性位置偏爱（CPP）和自身给药（SA）试验，在Sprague-Dawley大鼠中评估了MXE的滥用潜力（奖赏和强化作用）。此外，还分析了CPP条件化阶段的运动活动。氯胺酮用作参比药物。MXE（2.5和5mg/kg）在大鼠中诱导出显著的CPP，其效果与氯胺酮（5mg/kg）相当。有趣的是，MXE未产生任何运动改变，而氯胺酮降低了大鼠的运动活性。在SA试验中，大鼠对MXE（0.25、0.5、1.0mg/kg/输注）表现出适度的自身给药行为，而氯胺酮（0.5mg/kg/输注）则被大量自身给药。这些结果表明，与氯胺酮相似，MXE在大鼠中具有奖赏和强化作用。本研究强烈表明MXE具有人类滥用的潜力。此外，MXE和氯胺酮对运动活性和自身给药速率的不同影响表明，这些药物的精神药理作用在某些方面可能存在差异。更重要的是，本研究主张对MXE及其相关物质进行仔细监测并及时管控。
