化疗止吐药的研究进展

5-HT3受体拮抗剂恩丹司琼、托烷司琼、格拉司琼等通过与5-HT3受体结合，阻滞5-HT3受体而产生止吐作用。临床试验表明，5-HT3受体拮抗剂对于化疗急性呕吐有明显疗效，但对于延迟性呕吐作用较差。NK1受体拮抗剂通过与NK1受体结合，阻滞NK1受体而产生作用。临床试验表明，NK1受体拮抗剂对急性和延迟性呕吐均有效，与5-HT3受体拮抗剂合用可提高急性呕吐的疗效。本文综述了5-HT3受体拮抗剂和NK1受体拮抗剂的作用、作用机制及临床应用。     

某院门诊单次化疗预防性止吐用药调研

目的调查本院门诊单次化疗预防性使用止吐药物现状,为止吐药物的合理使用提供参考。方法依照2012年NCCN指南,对化疗方案中化疗药物的致吐等级和止吐药的品种选择、使用天数和联合用药情况进行调研分析。结果506例中、重度致吐化疗方案均选择了5-HT,受体拮抗剂,其中80％以上的病例联用了糖皮质激素;低致吐和微致吐化疗方案5-HT,受体拮抗剂的使用率分别为93．52％和25％,而甲氧氯普胺的使用率仅为0．6％和3．85％。中、重度致吐的单次化疗预防性止吐选用长效5-HT,受体拮抗剂共242例,其中单次给药210例（占86．78％）,连续2～3d给药32例（占13．22％）;选用短效5-HT,受体拮抗剂共243例,其中连续给药2—3d的仅为98例（占40．33％）,单次给药145例（占59．67％）。结论本院门诊单次化疗预防性使用止吐药物在品种选择,联合用药,及疗程等方面仍有待改善。     

5 HT3受体拮抗剂相关便秘的研究进展

5- HT3受体拮抗剂是恶性肿瘤患者在化疗过程中常用的止吐药,其大大缓解了中高致吐性的化疗药物所致呕吐的发生率,对化疗的疗效的提高和不良反应的减少起到重要作用。但是5- HT3受体拮抗剂所引起的便秘也不可忽视,便秘极大地影响了患者对化疗的依从性,给患者精神、躯体造成损害,是肿瘤患者额外的负担。目前,尚缺乏特异性防治5- HT3受体拮抗剂所致便秘的药物,而中医药防治5- HT3受体拮抗剂所致便秘是一种有效的治疗手段,值得进一步研究及推广。本文从5- HT3受体拮抗剂相关便秘的研究进展着手,为更好地防治5- HT3受体拮抗剂所致便秘提供参考。     

某院5-HT3受体拮抗剂防治CINV的合理性评价

目的：对我院5-HT3受体拮抗剂用于防治化疗引起的恶心呕吐的使用情况进行合理性评价,进一步提高临床化疗止吐药的合理使用。方法：从我院用药决策系统随机抽取2016年6-11月住院静脉化疗患者中使用5-HT3受体拮抗剂止吐的电子病历200例。从适应症、药品遴选、用法用量、综合止吐方案、药物相互作用、用药时机、给药途径等多方面进行处方点评。结果：不合理用药病历111例,占55.5%。药品遴选不合理13例,占6.5%,以肺癌和乳腺癌为著;用法用量不合理75份,占37.5%;联合用药不合理19例,占9.5%。9例存在2种以上不合理用药情况,占4.5%。14例高致吐风险级别综合止吐方案单用5-HT3受体拮抗剂不合理,占7.0%。结论：我院止吐药5-HT3受体拮抗剂的应用存在较多不合理使用情况,有必要规范临床合理使用5-HT3受体拮抗剂,促进临床合理用药。     

44例5-HT3受体拮抗剂不良反应文献分析

目的探讨5-羟色胺3(5-HT3)受体拮抗剂致药品不良反应(ADR)的特点及相关因素,为临床合理用药提供参考。方法利用"维普医药信息资源服务系统"、"万方数据医药信息系统"、"中华医学会全文期刊"、"中国医院数字图书馆",以"昂丹司琼"、"格拉司琼"、"托烷司琼"、"阿扎司琼"、"雷莫司琼"、"5-HT3受体拮抗剂"等为题名进行全面搜索,对2000年1月~2011年12月国内公开报道的5-HT3受体拮抗剂所致的ADR44例进行统计分析。结果 44例ADR患者中男性20例(45.45%),女性24例(54.55%),格拉司琼发生ADR的例数最高30例(68.18%),临床主要累及皮肤及附件、心血管系统、呼吸系统等。结论临床应高度重视5-HT3受体拮抗剂的ADR,以确保安全用药。     

帕洛诺司琼治疗化疗呕吐的临床研究进展

帕洛诺司琼是第一个获准用于预防迟发性化疗所致恶心、呕吐（chemotherapy-induced nausea and vomiting,CINV）的5-羟色胺3（5-HT3）受体拮抗剂。通过比较,发现帕洛诺司琼治疗急性期CINV至少同第一代5-HT3受体拮抗剂同样有效,对延迟性CINV的疗效优于第一代5-HT3受体拮抗剂。本文综述了帕洛诺司琼的临床研究进展,并探讨了多剂量给予帕洛诺司琼的安全性和有效性。     

化疗用止吐药及其最新研究进展

化疗所致恶心、呕吐(CINV)是癌症化疗最常见的不良反应之一,是影响化疗患者用药依从性和疗效的主要因素之一。本文简述了CINV的机制、早期的药物治疗和新型止吐药物(5-HT3受体拮抗剂),主要介绍近期问世的两类止吐新药———长效5-HT3受体拮抗剂和NK-1受体拮抗剂,并对其代表药物进行详细阐述。     

姜对链脲佐菌素致Ⅰ型糖尿病大鼠的治疗作用

姜Zingiber officinale的某些药理活性与其对5-羟色胺(5-HT)受体的作用有关，如链脲佐菌素(STZ)致糖尿病大鼠体内5-HT水平显著升高，5-HT诱导正常大鼠高血糖与特异性5-HT2A、5-HT3受体相关、以及这2个受体拮抗剂有益于改善糖尿病大鼠症状等。作者研究了姜对STZ致糖尿病大鼠血糖     

前置审方在围术期止吐药合理使用中的应用与思考

目的：分析前置审方系统对我院围术期止吐药合理使用的影响。方法：回顾统计某专科使用前置审方系统前后（2018年3月和2018年6月）围术期5-HT3受体拮抗剂的使用情况。结果：5-HT3受体拮抗剂医嘱不合理率由前置审方前的45.69%降至前置审方后的5.56%。不合理原因主要为2种5-HT3受体拮抗剂联用,其次是帕洛诺司琼超频率使用和托烷司琼超推荐剂量使用。结论：前置审方系统能有效促进临床合理用药。     

我院288例5-HT3受体拮抗剂用药分析

目的:了解我院5-HT3受体拮抗剂的临床应用情况,以期为临床合理用药提供参考.方法:采用回顾性研究的方法,随机抽取我院2021年1月 –2021年6月使用5-HT3受体拮抗剂的288例住院患者病历,收集患者性别、年龄、就诊科室、适应证、药品用法用量等信息进行统计分析.结果:288例患者中有72例(25.00％)存在不合...     

肿瘤化疗止吐剂格拉司琼透皮贴剂的研究进展

恶心与呕吐是癌症患者接受化疗后最常见的毒副作用,严重影响患者的生存质量和对化疗的依从性。5-羟色胺3(5-HT3)受体拮抗剂是目前最有效的止吐剂,临床以静脉注射或者口服的方式给药。格拉司琼透皮贴剂于2008年被美国FDA批准用于控制化疗患者恶心与呕吐,是首个上市的5-HT3受体拮抗剂透皮贴剂。本文根据国内外文献,对格拉司琼透皮贴剂的药学特点、药效学、药代动力学、临床研究近况及使用中存在的一些不足等进行综述。     

抗癌化疗止吐药的研究进展

目的：通过对5-HL受体阻断剂，NK-1受体阻断剂，皮质类固醇等药物的研究进展进行阐述，了解用于预防恶心呕吐的药物，为预防和治疗化疗后的恶心呕吐反应寻找或开发出更安全、有效、经济的药物，从而减少或避免在化疗过程中的依从性差，疗效不稳定等情况。方法：通过回顾性研究国内外相关的临床试验和调研相关的文献，展开对其作用机制、药代动力学、临床应用等方面的阐述。结果：5-HT3受体阻断剂和NK-1受体阻断剂对急性呕吐均有较好的疗效，但后者对延迟性呕吐的效果优于前者，而与皮质激素合用疗效会增加，减少不良反应。结论：5-HT3受体阻断剂广泛应用于临床，对急性呕吐有效，但这些止吐药不能做到完全控制化疗引起的恶心呕吐反应（chemotherapy-induced nausea and vomiting，CINV）。     

姜辣素在2种呕吐动物模型中止呕作用机制的探讨

Abstract: Objective To explore an antiemetic drug of ginger in order to supplement the antagonists of 5-hydroxytryptamine-3 receptor（5-HT3）and neurokinin-1 receptor（NK1）in clinical，which are endowed with single target，high price and serious side-effect. Methods A new vomiting model of mink as well as classic pica model of rat was established with specific 5-HT3 receptor agonist 1-phenylbiguanide hydrochloride and dopamine receptor agonist apomorphine. The inhibitive effect of gingerols on vomiting behavior of minks and kaolin pica consumption of rats was observed. Results Gingerols displayed distinguished inhibitive effect on vomiting behavior of minks and kaolin consumption of rats in a dose-dependent manner（P＜0.05）. Conclusions The study of gingerol in vomiting model of mink and pica model of rat suggests that gingerol exhibits antiemetic effect. The mechanisms may refer to the system of 5-hydroxytryptamine and dopamine receptors. The result indicates that gingerol is of latent applied value on the study of novel natural multitarget antiemetic drugs.     

Characterization of 5-hydroxytryptamine-induced depolarizations in rat isolated vagus nerve

An additional component of the depolarization induced by 5-hydroxytryptamine (5-HT) in the rat isolated vagus nerve has recently been attributed to activation of 5-HT₄ receptors. To confirm and extend this finding, extracellular recordings of D.C. potentials were made using the ‘grease-gap’ technique during continuous superfusion of the isolated nerve. Beginning at 1 nM, 5-HT induced small depolarizations that displayed a slow onset. At concentrations 1 μM, large depolarizations with rapid onset were elicited. In the presence of the 5-HT₃ receptor antagonists, granisetron or ondansetron, 5-HT responses were diminished and exhibited an increased latency to peak. These small, slow depolarizations were not reduced by 5-HT₁ or 5-HT₂ receptor antagonists, but were potently inhibited by the 5-HT₄ receptor antagonist GR 113808 (pA₂ = 9.3), and mimicked by 5-methoxytryptamine (pEC₅₀ = 5.3). 5-HT₄-mediated responses were larger at 37°C than at 31°C, but also showed marked diminution with repeated 5-HT applications at concentrations greater than 1 μM. Conversely, 5-HT₃ receptor responses were potentiated at lower temperatures (31°C). Consistent with the reported positive coupling of 5-HT₄ receptors to adenylyl cyclase, forskolin and 8-Br-cAMP produced slowly developing depolarizations which were qualitatively similar to 5-HT₄ receptor activation. Pre-depolarization of nerves with 10 μM forskolin or 300 μM 8-Br-cAMP diminished the effect of 5-HT₄ receptors. This study has confirmed the presence of 5-HT₄ receptors on the vagus nerve of the rat and defined some conditions that optimize their pharmacological isolation. The rat isolated vagus nerve constitutes a simple and robust preparation for studying 5-HT₄ receptors in the peripheral nervous system.     

2008—2010年复旦大学附属肿瘤医院5-羟色胺3受体阻断剂临床应用分析

目的:统计我院2008—2010年临床5-羟色胺3(5-HT3)受体阻断剂使用情况和发展趋势,探讨合理使用要点。方法:对我院3年来5-HT3受体阻断剂使用情况进行回顾性分析,统计药品的销售数量、金额、类别,分析临床用药趋势。结果:5-HT3受体阻断剂总体用量呈快速增长,品种使用显示出明显的变化趋势。结论:3年来5-HT3受体阻断剂总体用量增长,长半衰期品种受临床欢迎。     

Evidence that orexin-A-evoked grooming in the rat is mediated by orexin-1 (OX1) receptors, with downstream 5-HT2C receptor involvement

RATIONALE: Orexins A and B have recently been discovered and shown to be derived from preproorexin, primarily expressed in the rat hypothalamus. Orexin-A has been ascribed a number of in vivo functions in the rat after intracerebroventricular (ICV) administration, including hyperphagia, neuroendocrine modulation and, most recently, evidence for a behavioural response characterised by an increase in grooming. OBJECTIVES: Here, we have investigated the orexin-receptor subtypes involved in the grooming response to orexin-A (3 microg, ICV) in the rat. METHODS: Male rats, habituated to clear Perspex behavioural observation boxes, were pretreated with antagonists with mixed selectivity for OX1, OX2, 5-HT2B and 5-HT2C receptor subtypes prior to the administration of orexin-A and the intense grooming response elicited by this peptide assessed. RESULTS: Pretreatment of rats with a mixed OX1/5-HT2B/2C receptor antagonist 1-(4-methylsulfanylphenyl)-3-quinolin-4-ylurea (SB-284422), revealed a significant, but incomplete, blockade of orexin-A-induced grooming. Despite the low potency of orexin-A at 5-HT2B and 5-HT2C receptors in vitro (pKi<5), studies were undertaken to determine whether downstream 5-HT2B or 5-HT2C receptors mediate in the grooming-elicited by orexin-A. Whilst the selective 5-HT2B receptor antagonist, SB-215505 (3 mg/kg, PO, 5-HT2B, pKi=8.58; OX1, pKB < 5.15) failed to effect orexin-A-induced grooming, the selective 5-HT2C receptor antagonist, SB-242084 (1 mg/kg, IP, 5-HT2C, pKi = 8.95; OX1, pKB < 5.1) potently antagonised the grooming response to this peptide. This suggested that the partial blockade of orexin-A-induced grooming obtained with SB-284422 might be attributable to its 5-HT2C and/or OX1 receptor blocking activity. However, complete blockade of orexin-A-induced grooming by the subsequently identified selective OX1 receptor antagonist 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl urea hydrochloride, SB-334867-A (OX1, pKB = 7.4; OX2, pKB = 5.7), devoid of appreciable affinity for either 5-HT2B (pKi < 5.3) or 5-HT2C (pKi < 5.4) receptors, provides the first definitive evidence that a central behavioural effect of orexin-A (grooming) is mediated by OX1 receptors. CONCLUSIONS: This data suggests that orexin-A indirectly activates 5-HT2C receptors downstream from OX1 receptors to elicit grooming in the rat. The use of SB-334867-A in vivo will enable the role of OX,1 receptors within the rat central nervous system to be further characterised.     

THE CLASSIFICATION OF 5-HYDROXYTRYPTAMINE RECEPTORS

1. The current classification of receptors for 5-hydroxytryptamine (5-HT) is based on functional studies, and encompasses three main receptor types. 2. 5-HT1-like receptors mediate inhibition of release of various neurotransmitters from central and peripheral sites, smooth muscle contraction and relaxation (and release of endothelium-derived relaxing factor), tachycardia, a variety of behavioural actions (for example, forepaw treading, hypothermia, hyperphagia, drug discriminative stimulus properties, nociceptive pathway modulation, and anxiolytic, anti-aggressive and prosexual effects), and central neuronal excitatory and inhibitory activity. Selective antagonists for this receptor are not yet available, but the 5-HT2 receptor antagonists methysergide and methiothepin have appreciable affinity for 5-HT1-like receptors, and 5-carboxamidotryptamine is a selective agonist. 3. 5-HT2 receptors mediate smooth muscle contraction, platelet aggregation, increased capillary permeability, some behavioural syndromes (for example, head twitch and wet-dog shakes) and drug discriminative stimulus properties, central neuroexcitatory effects, and some neuroendocrine functions. Ketanserin and cyproheptadine are selective antagonists. 4. 5-HT3 receptors mediate peripheral afferent and efferent neuroexcitatory actions, anxiogenic effects, and modulation of cytotoxic drug-induced emesis, gastric emptying, and dopamine-related mesolimbic hyperactivity. Selective antagonists include cocaine, MDL 72222 and ICS 205-930; 2-methyl-5-HT is a selective agonist.     

Roles of serotonin receptor subtypes for the antinociception of 5-HT in the spinal cord of rats

The contribution of 5-HT (5-hydroxytryptamine) receptor subtypes to the antinociception produced by intrathecal 5-HT in the formalin test was investigated in rats. Intrathecal 5-HT suppressed both phases of behaviors produced by 5% formalin, and this was blocked by antagonists for 5-HT(1B) (3-[3-(Dimethylamino)propyl]-4-hy-droxy-N-[4-(4-pyridinyl)phenyl]benzamide dihydrochloride, GR 55562), 5-HT(2C) (N-ormethylclozapine/8-Chloro-11-(1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine, D-MC), 5-HT3 (1-Methyl-N-(8-methyl-8-azabicyclo[3.2.1]-oct-3-yl)-1H-indazole-3-carboxamide maleate, LY-278,584) and 5-HT4 receptors (4-Amino-5-chloro-2-metho-xy-benzoic acid 2-(diethylamino)ethyl ester hydrochloride, SDZ-205,557), but not the 5-HT(1D) receptor antagonist 3-[4-(4-Chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol hydrochloride (BRL 15572). The 5-HT(1A) receptor antagonist N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl]-N-2-pyridinyl-cyclohexanecarboxamide maleate (WAY-100635) decreased only the second phase antinociception of 5-HT. Intrathecal administration of agonists for 5-HT(1A) (3-(N,N-Dipropylaminoethyl)-1H-indole-5-carboxamide maleate, Dipropyl-5CT), 5-HT(1B) (7-Trifluoromethyl-4(4-met-hyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline maleate, CGS-12066A), 5-HT(2C) (6-Ch-loro-2-(1-piperazinyl)pyrazine hydrochloride, MK 212), 5-HT3 (N-(3-Chlorophenyl)imidodicarbonimidic diamide hydrochloride, m-CPBG) and 5-HT4 receptors (2-[1-(4-Piperonyl)piperazinyl]benzothiazole, BZTZ) suppressed both phases of the formalin response. The results of the present study indicate that spinal 5-HT(1B,) 5-HT(2C,) 5-HT3 and 5-HT4 receptors, but not the 5-HT(1D) receptor, mediate antinociception produced by 5-HT in the formalin test. The relevance of the 5-HT(1A) receptor is less clear because of the different effects of antagonist and agonist.