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 postoperative 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 5-HT₂ 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-HT_2C receptor agonist WAY-163909 but not by pretreatment with the mixed 5-HT_2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Moreover, the blockade of ketamine-induced hypothermia by WAY-163909 was reversed by pretreatment with the selective 5-HT_2C receptor antagonist SB-242084. These findings demonstrate that stimulation of 5-HT_2C 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 5-HT_2C receptor agonists.

2017-05-17·ACS Chemical Neuroscience3区 · 医学

A Potential PET Radiotracer for the 5-HT_2C Receptor: Synthesis and in Vivo Evaluation of 4-(3-[¹⁸F]fluorophenethoxy)pyrimidine

3区 · 医学

Article

作者: Kim, Juhyeon ; Cho, Yong Seo ; Choo, Hyunah ; Moon, Byung Seok ; Lee, Ho-Young ; Lee, Byung Chul ; Pae, Ae Nim ; Min, Sun-Joon ; Kim, Hak-Joong

The serotonin 2C receptor subtype (5-HT_2C) is an excitatory 5-HT receptor widely distributed throughout the central nervous system. As the 5-HT_2C receptor displays multiple actions on various neurotransmitter systems including glutamate, dopamine, epinephrine, and γ-aminobutyric acid (GABA), abnormalities of the 5-HT_2C receptor are associated with psychiatric diseases such as depression, schizophrenia, drug abuse, and anxiety. Up to date, three kinds of 5-HT_2C PET radiotracers such as [¹¹C]N-methylated arylazepine (1), [¹¹C]WAY-163909 (2), and [¹⁸F]fluorophenylcyclopropane (3) have been developed, but they may not be suitable for in vivo 5-HT_2C imaging study due to their modest specific binding. Herein, the synthesis and in vivo evaluation of 4-(3-[¹⁸F]fluorophenethoxy)pyrimidine [¹⁸F]4 as a potential PET radiotracer for the 5-HT_2C receptor is described. [¹⁸F]4 was synthesized by nucleophilic aromatic substitution of diaryliodonium precursor 17a with a 7.8 ± 2.7% (n = 6, decay corrected) radiochemical yield and over 99% radiochemical purity, showing an 89 ± 14 GBq/μmol specific radioactivity. The in vivo PET imaging studies of [¹⁸F]4 with or without lorcaserin, a U.S. Food and Drug Administration approved selective 5-HT_2C agonist, demonstrated that [¹⁸F]4 exhibits a high level of specific binding to 5-HT_2C receptors in the rat brain.

2010-06-01·Neuropharmacology2区 · 医学

Effects of serotonin (5-HT)2 receptor ligands on depression-like behavior during nicotine withdrawal

2区 · 医学

Article

作者: Andrew C. McCreary ; Magdalena Zaniewska ; Karolina Wydra ; Małgorzata Filip

A pronounced withdrawal syndrome including depressed mood prevents cigarette smoking cessation. We tested if blockade or activation of serotonin (5-HT)(2) receptors affected the time of immobility (as an indirect measure of depression-like behavior) in naïve animals and in those withdrawn from chronic nicotine in the forced swim test (FST). The antidepressant imipramine was used as a control. In the FST, the selective 5-HT(2A) receptor antagonist M100,907 (1-2 mg/kg, but not 0.5 mg/kg), the selective 5-HT(2C) receptor antagonist SB 242,084 (0.3-1 mg/kg, but not 0.1 mg/kg), the 5-HT(2C) receptor agonists Ro 60-0175 (10 mg/kg, but not 3 mg/kg) and WAY 163,909 (1.5-10 mg/kg, but not 0.75 mg/kg) as well as imipramine (30 mg/kg, but not 15 mg/kg) decreased the immobility time while the non-selective 5-HT(2) receptor agonist DOI (0.1-1 mg/kg) was inactive in naïve rats. We found an increase in immobility time in rats that were withdrawn from nicotine exposure after 5 days of chronic nicotine treatment. This effect increased from day 1 until day 10 following withdrawal of nicotine, with maximal withdrawal effects on day 3. M100,907 (1 mg/kg), SB 242,084 (0.3 mg/kg), Ro 60-0175 (3 mg/kg), WAY 163,909 (0.75-1.5 mg/kg) and imipramine (15-30 mg/kg) shortened the immobility time in rats that had been removed from nicotine exposure for 3 days. Locomotor activity studies indicated that the effects of SB 242,084 might have been non-specific, as we noticed enhanced basal locomotion in naïve rats. This data set demonstrates that 5-HT(2A) receptor antagonist and 5-HT(2C) receptor agonists exhibited effects similar to antidepressant drugs and abolished the depression-like effects in nicotine-withdrawn rats. These drugs should be considered as adjuncts to smoking cessation therapy, to ameliorate abstinence-induced depressive symptoms.

100 项与 WAY-163909 相关的药物交易

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