The serotonin 2C receptor agonist WAY-163909 attenuates ketamine-induced hypothermia in mice.
The serotonin 2C receptor agonist WAY-163909 attenuates ketamine-induced hypothermia in mice.
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DOI：
10.1016/j.ejphar.2018.11.003
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发表时间：
2019-01-05
影响因子：
5
通讯作者：
Murnane KS
中科院分区：
文献类型：
--
作者：
Murphy TJ;Murnane KS
据报道，麻醉诱导的低温(AIH)是许多术后不良反应的原因，包括死亡率增加，免疫反应降低，心脏事件，以及更多的手术伤口感染。在某些情况下，可以通过预热液体和气体以及强制空气加热系统将AIH降至最低，但此类技术并不总是有效的，可能会导致患者烧伤或其他不良影响。据报道，刺激5-HT2受体可通过多种机制升高体温，因此，可能是从药物上最小化AIH的一个可行的靶点。在本研究中，我们用直肠测温的方法观察了刺激5HT2受体对注射麻醉剂氯胺酮引起的低体温的影响。我们报告了氯胺酮剂量依赖性地诱导体温降低，在每周间隔一次的三次注射过程中，小鼠对氯胺酮的这种影响没有耐受性。选择性5-HT2C受体激动剂Way-163909可显著减轻氯胺酮引起的体温过低，而混合型5-HT2A/2C受体激动剂2，5-二甲氧基-4-碘苯丙胺不能显著减轻氯胺酮引起的体温过低。选择性5-HT2C受体拮抗剂SB-163909可逆转氯胺酮诱导的降温效应。这些发现表明，刺激5-HT2C受体可以减少AIH，至少对氯胺酮诱导的低温是有效的。他们需要进一步研究这种相互作用背后的药理学和神经生物学机制，并将其推广到其他麻醉剂。此外，这些发现表明，术中维持体温可能是5HT2C受体激动剂的一种新的临床用途。
Anesthesia-Induced Hypothermia (AIH) has been reported to be the cause of many postoperative adverse effects, including increased mortality, decreased immune responses, cardiac events, and a greater prevalence of surgical wound infections. AIH can in some cases be minimized with pre-warming fluids and gases and forced-air heating systems, but such techniques are not always effective and can result in patient burns or other adverse effects. Stimulation of 5-HT2 receptors has been reported to increase body temperature through a variety of mechanisms, and as such, may be a viable target for pharmacologically minimizing AIH. In the present study, we examined the effects of 5HT2 receptor stimulation on hypothermia induced by the injectable anesthetic ketamine in Swiss-Webster mice using rectal thermometry. We report that ketamine dose-dependently induced hypothermia, and mice did not become tolerant to this effect of ketamine over the course of three injections spaced at once per week. Ketamine-induced hypothermia was significantly attenuated by pretreatment with the selective 5-HT2C receptor agonist WAY-163909 but not by pretreatment with the mixed 5-HT2A/2C receptor agonist 2,5dimethoxy-4-iodoamphetamine (DOI). Moreover, the blockade of ketamine-induced hypothermia by WAY-163909 was reversed by pretreatment with the selective 5-HT2C receptor antagonist SB-242084. These findings demonstrate that stimulation of 5-HT2C receptors can reduce AIH, at least for ketamine-induced hypothermia. They warrant further study of the pharmacological and neurobiological mechanisms underlying this interaction and its extension to other anesthetics. Furthermore, these findings suggest that the maintenance of body temperature during surgery may be a new clinical use for 5HT2C receptor agonists.
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影响因子：
7.3
作者：
FAHIM, I;ISMAIL, M;OSMAN, OH
通讯作者：
OSMAN, OH
影响因子：
8.8
作者：
Kabbara, A;Goldlust, SA;Pinchak, AC
通讯作者：
Pinchak, AC
影响因子：
2.9
作者：
LEFEUVRE, RA;AISENTHAL, L;ROTHWELL, NJ
通讯作者：
ROTHWELL, NJ
DOI：
10.1124/jpet.106.106989
发表时间：
2007-01-01
影响因子：
3.5
作者：
Marquis, Karen L.;Sabb, Annmarie L.;Rosenzweig-Lipson, Sharon
通讯作者：
Rosenzweig-Lipson, Sharon
DOI：
10.1124/jpet.110.166595
发表时间：
2010-08-10
影响因子：
3.5
作者：
Murnane, K. S.;Fantegrossi, W. E.;Howell, L. L.
通讯作者：
Howell, L. L.