Network meta-analysis of triple therapy for the prevention and treatment of acute nausea and vomiting caused by emetogenic chemotherapy drugs with moderate and high risk / 中国药房

OBJECTIVE To evaluate the efficacy of the triple therapy of 5-HT3 receptor antagonists， neurokinin-1 receptor antagonists and dexamethasone （referred to as “triple therapy”） in the prevention and treatment of acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI and Wanfang data， randomized controlled trials （RCTs） about triple therapy or 5-HT3 receptor antagonist combined with dexamethasone （referred to as “dual therapy”） were collected during the inception to May 2023. After literature screening， data extraction and literature evaluation， network meta-analysis was performed by using Stata 16.0 software. RESULTS A total of 59 RCTs were included， involving 23 418 patients and 15 interventions. Results of network meta-analysis showed that fosaprepitant + palonosetron + dexamethasone （FPD） was most effective in terms of acute nausea and vomiting control rate， followed by fosaprepitant + granisetron + dexamethasone （FGD） and aprepitant + ramosetron + dexamethasone （AMD）. In terms of acute nausea control rate， FPD was the most effective， followed by aprepitant + palonosetron + dexamethasone （APD） and FGD. In terms of acute vomiting control rate， FPD was the most effective， followed by FGD and APD. CONCLUSIONS Fosaprepitant + palonosetron + dexamethasone is better than other triple therapy or dual therapy in preventing acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs.

Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

5-Hydroxytryptamine (5-HT) type 3 receptor (5-HT3R) is the only type of ligand-gated ion channel in the 5-HT receptor family. Through the high permeability of Na+, K+, and Ca2+ and activation of subsequent voltage-gated calcium channels (VGCCs), 5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system (CNS). 5-HT3Rs are widely expressed in the medial prefrontal cortex (mPFC), amygdala (AMYG), hippocampus (HIP), periaqueductal gray (PAG), and other brain regions closely associated with anxiety reactions. They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions. 5-HT3Rs mediate the activation of the cholecystokinin (CCK) system in the AMYG, and the γ‍-aminobutyric acid (GABA) "disinhibition" mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons (IINs). In contrast, a 5-HT3R-induced GABA "disinhibition" mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects. 5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG. This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs. However, given the circuit specific modulation of 5-HT3Rs on emotion, systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety, which deeply hinders the current clinical application of 5-HT3R drugs. Therefore, the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

Evaluation of antidepressant activity of ondansetron in rodent models of depression

Background: At present, there is an escalating concern regarding possible role of 5-HT3 receptor in psychopharmacology and the therapeutic potential of their antagonists. Moreover, inclusion of 5-HT3 receptor antagonist may curtail the antidepressant-induced LTP decrease causing memory deficits, thereby improving efficacy of current antidepressants. Aim and Objective: This study aims to evaluate the antidepressant activity of 5-HT3 antagonist, that is, ondansetron (OND) in rodent models of depression. Materials and Methods: Male Swiss albino mice (20–30 g bw) and Wistar rats (100–200 g bw) were divided into five groups. Animals received either OND p.o. (0.1, 0.5 and 1 mg/kg), venlafaxine (10 mg/kg), or vehicle (1 ml distilled water p.o.) in control. Tail suspension and forced swim test were used to evaluate the effects of drugs and control after 60 min of their administration. Furthermore, assessment of locomotor activity (LA) was done by photoactometer after 24 h of drug administration. Results: Ondansetron exhibited significant antidepressants activity (P < 0.05) in rodent models. However, LA was not significantly altered by OND. Conclusion: Ondansetron exhibited significant antidepressant activity in rodent models hence paving the way for exploration of 5-HT3 receptor antagonist in future researches and its therapeutic application in depression.

Comparison of Intravenous Ramosetron and Ondansetron as Prophylaxis for Postoperative Nausea and Vomiting following General Anesthesia

Objective: To compare the efficacy and side effects of 5HT3 antagonists, ramosetron, and ondansetron as prophylaxis for postoperative nausea and vomiting (PONV) following general anesthesia. Materials and Methods: One hundred and ten patients of the American Society of Anesthesiology Grade I–II, between the age group of 18 to 60 years weighing 40 to 70 kg, undergoing general anesthesia were studied. Group 1 received ramosetron 0.3 mg intravenous (IV) and Group 2 received ondansetron 8 mg IV 15 min before the end of surgery. The incidence of PONV, need for rescue antiemetic, and side effects were evaluated in both the groups. QTc interval prolongation was also evaluated in both the groups by taking electrocardiograms at regular intervals. Results: This study showed that there was no statistically significant difference in the incidence of PONV between the ondansetron group and the ramosetron group during the first 24 h after surgery. For PONV score of ?2 during the first 6 h, the incidence was 3.59% and 1.81% for ramosetron and ondansetron, respectively, and during 6–24 h, the incidence was 1.81% for both the drugs. Conclusion: IV ramosetron 0.3 mg is as effective as IV ondansetron 8 mg in preventing PONV in patients undergoing general anesthesia

Role of 5-HT 1A and 5-HT 3 receptors in sevoflurane-induced cerebral neurotoxicity in aged rats / 中华麻醉学杂志

Objective:To preliminarily investigate the relationship between the mechanism of sevoflurane-induced cerebral neurotoxicity and receptors of 5-HT 1A and 5-HT 3 in aged rats. Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 18-20 months, weighing 600-750 g, were divided into 3 groups ( n=8 each) using a random number table method: group C, group LS and group HS.In group C, group LS and group HS, 50% O 2, 1.5% sevoflurane plus 50% O 2 and 3% sevoflurane plus 50% O 2 were inhaled for 2 h, respectively.Open field test was performed at 1 day before inhalation of sevoflurane and at 1 day after the end of inhalation, the time spent in the central square, the number of crossing the grid and the number of standing on the back legs were recorded.The Morris water maze test was performed at 6 days before inhalation of sevoflurane and at 1 day after the end of inhalation, the escape latency, the total swimming distance and the number of crossing the platform were recorded.Immediately after the end of behavioral testing, the hippocampal tissues were obtained for determination of 5-HT 1A and 5-HT 3 receptors mRNA expression and the number of positive cells (using real-time reverse transcription-polymerase chain reaction assay and immunohistochemical method). Results:Compared with group C, the time spent in the central square was significantly prolonged, the number of crossing the grid and the number of standing on the back legs were decreased, the escape latency was prolonged, the total swimming distance was increased, the number of crossing platform was decreased, the mRNA expression of 5-HT 1A and 5-HT 3 was down-regulated, and the number of positive cells was decreased in HS group ( P<0.05). Conclusion:The mechanism of cerebral neurotoxicity induced by sevoflurane may be related to the down-regulation of the activities of 5-HT 1A and 5-HT 3 receptors in aged rats.

Comparison of effects of electroacupuncture at "Tianshu" (ST25) and "Dachangshu" (BL25) on intestinal sensitivity and expression of muscarinic M3R and 5-HT3AR in irritable bowel syndrome rats / 针刺研究

OBJECTIVE: To observe and compare the effect of electroacupuncture (EA) of "Tianshu" (ST25) and "Dachangshu" (BL25) on intestinal sensitivity and the expression of M3 muscarinic acetylcholine receptor (M3R) and 5-hydroxytryptamine 3A receptor (5-HT3AR) in the colon tissue in irritable bowel syndrome (IBS) rats, so as to explore its mechanism underlying improvement of IBS. METHODS: Forty newborn Wistar rats were randomly divided into blank control, model, ST25 and BL25 groups (n＝10 rats per group). The IBS model was established by joint application of maternal separation, acetic acid enema plus colorectal distension from day 8 to 21 after birth. At the age of 9 weeks, EA (2 Hz/100 Hz, 0.1－0.3 mA) was applied to ST25 and BL25 for 20 min, once every other day for 5 times. The modified method was used to record the abdominal withdrawal reflex (AWR), so as to evaluate the visceral sensitivity by referring to the modified Al-Chaer's and colleagues' methods. The threshold (initial wave), the number and peak-peak value of contraction waves (AWR) within 90 s were recorded. The immunoactivity of M3R and 5-HT3AR in the colon tissue was detected by immunohistochemistry. RESULTS: After modeling, the latency was obviously shortened, the number and peak-peak values of contraction waves of intestine were significantly increased, and the immunoactivity of M3R and 5-HT3AR was notably up-regulated in the model group compared with the blank control group (P<0.01). After the EA intervention, the latency was obviously prolonged, the peak-peak value in both ST25 and BL25 groups, and the number of contraction waves in the ST25 group were significantly decreased (P<0.01), and the expression levels of M3 and 5-HT3A R were considerably down-regulated in both ST25 and BL25 groups relevant to the model group (P<0.01). The therapeutic effects were significantly better in the ST25 group than in the BL25 group in prolonging the latency and reducing the contraction wave number, and in down-regulating the expression of colonic M3R and 5-HT3AR (P<0.05, P<0.01). CONCLUSION: EA at ST25 and BL25 can reduce the intestinal sensitivity in IBS rats, which is probably associated with its effects in down-regulating the expression of M3R and 5-HT3AR in the colon. The therapeutic effects of ST25 were obviously better than those of BL25 in suppressing intestinal sensitivity and expression of colonic M3R and 5-HT3AR.

Network Meta-analysis of 5-HT3 Receptor Antagonists for Prevention of Acute Nausea and Vomiting Caused by High-dose Chemotherapy / 中国药学杂志

OBJECTIVE: To evaluate the efficacy of 5-HT3 antagonists in the prevention of acute nausea and vomiting caused by high-dose chemotherapy using the network Meta-analysis system. METHODS: Developing retrieval strategies, system retrieves electronic databases such as Pubmed, EMbase, Cochrane Library, VIP, Wanfang and CNKI (as of October 2018), to find a randomized controlled trial (RCT) that uses 5-HT3 receptor antagonist alone to prevent nausea and vomiting caused by high-dose chemotherapy in adults. Quality assessment and data extraction were performed on eligible RCTs, with outcomes including acute nausea and vomiting. The RESULTS of the included RCT studies were combined using traditional STA analysis and network Meta-analysis using STATA13.0 software and WINBUG software.The RESULTS of the included RCT studies were combined using traditional Meta-analysis and network Meta-analysis. RESULTS: A total of 20 studies were included, involving a total of 4 042 patients with high-dose emetogenic chemotherapy.Seven interventions were included (granstron, ondansetron, ramosetron, tropisetron, dolasetron, azasetron, and palonosetron) with a total arm count of 41.The traditional Meta RESULTS showed that palonosetron was more effective in preventing acute nausea and vomiting caused by high-dose chemotherapy than ondansetron, and the difference was statistically significant (P0.05). Ondansetron may be inferior to granisetron (OR=1.238), but the difference is not statistically significant (P>0.05).For acute nausea caused by high-dose chemotherapy, ondansetron may be inferior to granisetron (OR=1.232), but the difference was not statistically significant (P>0.05).Ramosetron may be better than granisetron (OR=0.632), but the difference was not statistically significant (P>0.05).Network Meta-analysis found that ondansetron was inferior to palonosetron in the treatment of acute vomiting due to high-dose chemotherapy (OR=0.60, 95%CI:0.39-0.88). Palonosetron was superior to ramosetron (OR=2.54, 95% CI:1.16-5.80). SCURA RESULTS showed that the best treatment for acute nausea caused by high-dose chemotherapy was palonosetron, followed by ramosetron, dolasetron, ondansetron, granisetron and tropisetron. The best treatment for acute vomiting caused by high-dose chemotherapy is palonosetron, followed by ramosetron, azasetron, dolasetron, tropisetron, granisetron and ondansetron. The RESULTS of the network Meta-analysis are basically consistent with those obtained by traditional Meta-analysis. CONCLUSION: Compared with the first-generation 5-HT3 receptor antagonist, palonosetron is more effective in preventing acute nausea and vomiting caused by high-dose chemotherapy, ramosetron is more effective than other first-generation 5-HT3 receptor antagonists. Whether the RESULTS of this study will guide the clinical practice still requires a large-scale prospective study designed specifically to verify.

Regulatory Actions of Intestines-unblocking and Turbid-purging Recipe on Colonic 5-Hydroxytryptamine and Its Receptor in Rats with Constipation-dominant Irritable Bowel Syndrome / 广州中医药大学学报

Objective To investigate the regulatory actions of Intestines-unblocking, Turbid-purging Recipe (ITR) on colonic 5-hydroxytryptamine (5-HT) and its receptor 5-hydroxytryptamine 3 (5-HT3) in rats with constipation-dominant irritable bowel syndrome (IBS-C), and to explore the therapeutic mechanism of ITR in treating IBS-C. Methods Forty-two male SD rats were randomly divided into 6 groups, namely normal group, model group, western medicine group, high-, middle- and low-dose Chinese medicine groups, 7 rats in each group. IBS-C rat model was established by intragastric administration of ice water. After establishment of the model, western medicine group was given intragastric administration of Cisapride Tablets (at the dosage of 3.6 mg·kg-1·d-1), Chinese medicine groups were given intragastric administration of various dosages of ITR granules (18.5, 9.25, 4.625 g·kg-1·d-1 respectively) , and the model group was given intragastric administration of normal saline, the treatment lasting 14 d. The rats in various groups were given normal feeding and drinking. After treatment, HE staining method was used to observe pathological changes in the intestinal tissue, immunohistochemistry method was used to observe the expression levels of intestinal 5-HT and 5-HT3 receptor. Results Compared with the normal group, the expression level of rat intestinal 5-HT was increased (P < 0.05) and that of 5-HT3 receptor was decreased (P < 0.05) in the model group and the medication groups. Compared with the model group, 5-HT expression level was decreased significantly (P<0.05) and 5-HT3 receptor expression level was increased (P < 0.05) in the medication groups, and the improvement of the middle-dose Chinese medicine group was more obvious (P < 0.05). Conclusion ITR has therapeutic efficacy for IBS-C rats through lowering 5-HT expression and increasing 5-HT3 receptor expression, which results into the improvement of intestinal sensitivity and abnormal dynamic of the rats.

Clinical analysis of aprepitant for treating vomiting caused by cis-platin regimen / 重庆医学

Objective To investigate the clinical efficacy of aprepitant in the treatment of cisplatin based chemotherapy in-duced nausea and vomiting.Methods The tumor patients treated with cisplatin(80 mg/m2)chemotherapeutic regimen in Affiliated Shantou Hospital of Sun Yat-Sen University from December 1,2014 to December 1,2016 were selected,61 cases still had vomiting after using granisetron and dexamethasone for routinely stopping vomiting,the patients with aprepitant and dexamethasone for fur-ther stopping vomiting served as the aprepitant group,while the patients with granisetron and dexamethasone as the granisetron group.Then the complete response(CR)rates within 24,24-72,>72-144 h were observed in the two groups.Results The CR rates within 24 h in the aprepitant group and granisetron group were 66.67% and 51.61% respectively,the difference was not sta-tistically significant(P=0.232),which at 24-72 h were 80.00% and 54.84% respectively,the aprepitant group was significantly better than the granisetron group(P=0.036),which at >72-144 h were 86.67% and 64.52% respectively,the aprepitant group was better than the granisetron group(P=0.045).The comparison of adverse reactions between the two antiemetic drugs found that constipation,diarrhea,urticaria,fatigue and anxiety had no significant difference(P>0.05),the occurrence rate of total adverse reactions in the aprepitant group was 23.33%,which in the granisetron group was 25.81%,the difference between the two groups was not statistically significant(P>0.05).Conclusion Aprepitant combined with dexamethasone has better effect for treating hy-peremetic chemotherapy drug cisplatin chemotherapy caused nausea and vomiting with good tolerance.

Lamotrigine, an antiepileptic drug, inhibits 5-HT₃ receptor currents in NCB-20 neuroblastoma cells

Lamotrigine is an antiepileptic drug widely used to treat epileptic seizures. Using whole-cell voltage clamp recordings in combination with a fast drug application approach, we investigated the effects of lamotrigine on 5-hydroxytryptamine (5-HT)₃ receptors in NCB-20 neuroblastoma cells. Co-application of lamotrigine (1~300 µM) resulted in a concentration-dependent reduction in peak amplitude of currents induced by 3 µM of 5-HT for an IC₅₀ value of 28.2±3.6 µM with a Hill coefficient of 1.2±0.1. These peak amplitude decreases were accompanied by the rise slope reduction. In addition, 5-HT₃-mediated currents evoked by 1 mM dopamine, a partial 5-HT₃ receptor agonist, were inhibited by lamotrigine co-application. The EC₅₀ of 5-HT for 5-HT₃ receptor currents were shifted to the right by co-application of lamotrigine without a significant change of maximal effect. Currents activated by 5-HT and lamotrigine co-application in the presence of 1 min pretreatment of lamotrigine were similar to those activated by 5-HT and lamotrigine co-application alone. Moreover, subsequent application of lamotrigine in the presence of 5-HT and 5-hydroxyindole, known to attenuate 5-HT₃ receptor desensitization, inhibited 5-HT₃ receptor currents in a concentration-dependent manner. The deactivation of 5-HT₃ receptor was delayed by washing with an external solution containing lamotrigine. Lamotrigine accelerated the desensitization process of 5-HT₃ receptors. There was no voltage-dependency in the inhibitory effects of lamotrigine on the 5-HT3 receptor currents. These results indicate that lamotrigine inhibits 5-HT₃-activated currents in a competitive manner by binding to the open state of the channels and blocking channel activation or accelerating receptor desensitization.

Effect of Paeoniae Alba Radix extract on 5-HT3 receptor pathway in primarily cultured rat hippocampal neurons / 中草药

Objective: To investigate the effects of Paeoniae Alba Radix extracts (PAREs) on 5-HT3R mediated ion channels in primarily cultured hippocampal neurons of rats with depression. Methods: An animal model of depression was successfully developed and evaluated in rats. PARE was used for drug intervention. Serum in each group was collected, inactivated and then added into the primary hippocampal neurons for 24 h. The protein expression levels of 5-HT3AR and 5-HT3BR in the neurons of each group were examined by Western blotting (WB). The 5-HT3R channel current was recorded by a whole-cell patch clamp. Results: Compared with normal rats, the rats with depression had significantly reduction in total distance of the open-field test (OFT) and sucrose preference ratio (P < 0.01). The hippocampal neurons treated with serum of depressive rats had significantly increased protein expression of 5-HT3AR and 5-HT3BR (P < 0.05) and current density value (P < 0.05) compared to those treated with normal rat serum. Compared with the depressive rats, the rats treated with PARE and fluoxetine had significantly increased OFT (P < 0.05) and sucrose preference ratio (P < 0.01). The primary hippocampal neurons cultured with serum from PARE and fluoxetine-treated rats had significantly reduction in protein expression of 5-HT3AR and 5-HT3BR (P < 0.05, 0.01, 0.001) and current density value (P < 0.01). Conclusion: PARE can reduce the 5-HT3R ion channel current density in the rats with depression. This may be its central mechanism in treating depression.

Efficacy and safety of multiple-dose 5-HT3 receptor antagonists in preventing multi-day-based and highly emetogenic chemotherapy-induced nausea and vomiting / 中国肿瘤临床

Objective:To evaluate efficacy and safety of multiple-dose tropisetron plus dexamethasone (DXM) versus palonosetron plus DXM for chemotherapy-induced nausea and vomiting. (CINV) in patients received multiple day-based highly emetogenic chemotherapy. Methods:Cancer patients who were receiving multiday-based highly emetogenic chemotherapy were randomly assigned to AB or BA groups. A randomized, cross self-control ed method was applied. Patients in AB group received palonosetron (0.25 mg) 30 min before chemotherapy on day 1 and 3 or additional day 5 in the first cycle;and with tropisetron (5 mg) 30 min before chemotherapy on day 1, 2, and 3, or sup-plementary days (day 4 and 5) in the second cycle. Patients in BA group were treated with tropisetron in the first cycle and with palonosetron in the second cycle. Tropisetron and palonosetron were administered with DXM (10 mg) on day 1, followed by additional doses (5 mg) on days 2 to 5. Palonosetron group comprised patients in the AB group in the first cycle and BA group in the second cycle, whereas tropisetron group included patients in the AB group in the second cycle and BA group in the first cycle. Efficacy and safety of tropisetron versus palonosetron in preventing CINV were evaluated. Results:Ninety-one patients were included in analyses. At day 3, 4, and 5, incidence rates of nausea in the palonosetron group reached 28.6%, 30.8%, and 24.2%, respectively, and those of the tropisetron group totaled 42.8%, 47.3%, and 39.6%, respectively (P<0.05). At day 4, 5, and 6, incidence rates of vomiting in the palonosetron group measured 28.6%, 18.7%, and 5.5%, respectively, and those of the tropisetron group reached 42.9%, 34.1%, and 14.3%, respectively (P<0.05). From day 4 to day 5, day 6 to day 7, and day 1 to day 7, the palonosetron group yielded significantly lower incidence rates of nausea and vomiting than tropisetron group (P<0.05). Rate of rescue treatment in the palonosetron group was lower than that in tropisetron group (13.2%vs. 24.2%, P=0.057). No statistical difference in toxicities was observed between the two groups. Conclusion:Palonosetron plus DXM features better efficacy than that of tropisetron plus DXM against delayed CINV induced by multiple day-based highly emetogenic chemotherapy, which was well tolerated in the two treatments.

Tropisetron for the prevention of postoperative nausea and vomiting：a Meta-analysis / 重庆医学

Objective To evaluate the efficacy and safety of tropisetron for the prevention of postoperative nausea and vomi -ting (PONV) after general anesthesia .Methods We searched the PubMed ,EBSCO ,Cochrane ,CNKI and Weipu database to identi-fy randomized controlled trials (RCT ) about tropisetron in preventing PONV after general anesthesia .The methodological quality of the included RCT was assessed and data were extracted .The meta-analyses were performed by Rev Man5 .0 software .Results A total of 18 RCT met the inclusion criteria ,involving 2 901 patients .All RCT were randomized double-blind experiments .The results of meta-analyses showed that :(1)tropisetron could significantly decrease the incidence of PONV after general anesthesia ,[OR =0 .43 ,95% CI(0 .33 - 0 .57)] ,the efficacy in later period [OR = 0 .41 ,95% CI(0 .25 - 0 .65)] was better than that in earlier period [OR = 0 .66 ,95% CI(0 .44 - 0 .98)] ;(2)compared with tropisetron ,the combination of tropisetron and dexamethasone could signifi-cantly decrease the incidence of PONV [OR = 0 .37 ,95% CI(0 .22 - 0 .64)] ;(3)compared with granisetron or ondansetron ,tropise-tron could not significantly decrease the incidence of PONV ,the OR was [OR = 1 .08 ,95% CI(0 .68 - 1 .73)] and [OR = 0 .77 ,95%CI(0 .27 - 2 .21)] respectively ;(4)compared with dexamethasone ,tropisetron could not significantly decrease the incidence of PONV [OR = 1 .06 ,95% CI(0 .49 - 2 .30)] .Conclusion Tropisetron can significantly decrease the incidence of PONV after general anesthesia .It has also the advantage of decreasing incidence of the incidence of PONV combined with other non-5 HT-3 receptor in-hibitor such as dexamethasone .

Association of the Serotonin Receptor 3E Gene as a Functional Variant in the MicroRNA-510 Target Site with Diarrhea Predominant Irritable Bowel Syndrome in Chinese Women

BACKGROUND/AIMS: The functional variant (rs56109847) in the 3'-untranslated regions (3'-UTR) of the serotonin receptor 3E (HTR3E) gene is associated with female diarrhea predominant irritable bowel syndrome (IBS-D) in British populations. However, the relationship of the polymorphism both to HTR3E expression in the intestine and to the occurrence of Chinese functional gastrointestinal disorders has yet to be examined. METHODS: Polymerase chain reaction amplification and restriction fragment length polymorphism analyses were employed to detect polymorphisms among Chinese Han women, particularly 107 patients with IBS-D, 99 patients with functional dyspepsia (FD), 115 patients with mixed IBS and 69 patients with IBS-D + FD. We also assessed microRNA-510 (miR-510) and HTR3E expression in human colonic mucosal tissues with immunohistochemistry and other methods. Dual-luciferase reporter assays were conducted to examine the binding ability of miR-510 and HTR3E 3'-UTR. RESULTS: Genotyping data showed the variant rs56109847 was significantly associated with IBS-D, but not with FD, mixed-IBS, or FD + IBS-D. HTR3E was abundantly expressed around the colonic mucosal glands but less expressed in the stroma. miR-510 expression decreased, whereas HTR3E expression increased in the colonic mucosal tissue of patients with IBS-D compared with those in controls. HTR3E expression was significantly higher in patients with the GA genotype than that in patients with the GG genotype. The single-nucleotide polymorphisms disrupted the binding site of miR-510 and significantly upregulated luciferase expression in HEK293 and HT-29 cells. CONCLUSIONS: The single-nucleotide polymorphisms rs56109847 led to reduced microRNA binding and overexpression of the target gene in intestinal cells, thereby increasing IBS-D risk in the Chinese Han population. The decreased expression of miR-510 might contribute to IBS-D.

Retrospective analysis of the clinical rational drug use refer to NCCN antiemetic guideline / 中国药学杂志

OBJECTIVE: To investigate the application of antiemetics in patients with gynecological cancers during chemotherapy. METHODS: Medical records of 182 patients receiving chemotherapy lor gynecological cancer were evaluated and a descriptive a-nalysis was carried out.Logistic regression was performed to determine the predictors of compliance. RESULTS: The rate of adherence to guideline (CINV) for patients receiving one-day chemotherapy is 80%. prophylactic usage rate in patients receiving multi-days chemotherapy is 95%, with a 47% 5-HT3 receptor antagonist.The adherence to NCCN anti-emesis guideline was better in patients having paclitaxel-based chemotherapy than patients having no paclitaxel. CONCLUSION: As the biggest cancer hospital in China, antiemetics were commonly given as prevention of CINV in the form of 5-HT3 receptor antagonist, but antiemetic effect of dexametha-sone was ignored and needed to be emphasized.

Effects of Radix Paeoniae Alba Extract on Distribution and Expression of 5-HT3A/3B R in Frontal Lobe of Premenstrual Syndrome Rat Model with Liver-qi Depression Pattern / 世界科学技术-中医药现代化

This study was aimed to elucidate the 5-HT3R molecular mechanism of Radix Paeoniae Albaextract (RPAE) as drug intervention in the treatment of premenstrual syndrome (PMS) model rats with liver-qi depression pattern.PMS model rats with liver-qi depression pattern were prepared.And then,the model was treated with RPAE.The protein distribution of 5-HT3AR and 5-HT3BR in the frontal lobe was evaluated by the immune fluorescence technology and western blot.The results showed that there were positive expressions of 5-HT3AR and 5-HT3BR in frontal lobe of rats in each group.Compared with the normal group,the 5-HT3AR and 5-HT3BR protein expression levels of the frontal lobe in the model group increased significantly (P < 0.05).Compared with the model group,the 5-HT3AR protein expression level in the frontal lobe decreased significantly after RPAE treatment (P < 0.05).In conclusion,RPAE regulated the protein expressions of 5-HT3AR and 5-HT3BR in frontal lobe,which may be one of the mechanisms for its treatment of PMS with liver-qi depression pattern.

Effect of Radix Bupleuri Extract on 5-HT3R Pathway in Primarily Cultured Rat Hippocampal Neurons / 世界科学技术-中医药现代化

This study was aimed to investigate the effect of Radix Bupleuri extract (RBE) on 5-HT3R channel currents of primarily cultured hippocampal neurons in depression emotion rats.Depression emotion model ratswere duplicated.RBE was used for drug intervention.And then,the rats were evaluated by the open-field test (OFT) and the sucrose preference test.Serum of rats in each group was collected and then added into the primary cultured hippocampal neurons for 24 h.The 5-HT3R channel currents were recorded by the whole-cell patch clamp.The results showed that compared with the normal group,the total score of OFT in the model group was significantly decreased (P < 0.01); the sucrose preference ratio decreased obviously (P < 0.01); and the current density value of primary cultured hippocampal neurons in serum of the model group was significantly higher (P <0.01).Compared with the model group,the total scores of OFT in the RBE group and fluoxetine group increased significantly (P < 0.05,P < 0.01); the sucrose preference ratio also increased obviously (P < 0.05,P < 0.05); and current density value of the primary cultured hippocampal neurons in serum of the RBE group and fluoxetine group decreased significantly (P < 0.01,P < 0.01).It was concluded that RBE can effectively correct the abnormal 5-HT3R channel currents of rats with depression emotion,which may be one of the central mechanisms in the treatment of depression emotion.

Palonosetron versus granisetron in combination with aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with gynecologic cancer / 부인종양

OBJECTIVE: There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT3 receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC. METHODS: We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT3 receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT3 receptor and dexamethasone with/without aprepitant. RESULTS: When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT3 receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT3 receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001). CONCLUSION: The addition of aprepitant therapy was more effective than the control therapy of a 5-HT3 receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.

Association of 5-HT3B Receptor Gene Polymorphisms with the Efficacy of Ondansetron for Postoperative Nausea and Vomiting

PURPOSE: Postoperative nausea and vomiting (PONV) is a common problem after general anesthesia. Although 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists have significantly reduced PONV, over 35% of patients treated with ondansetron can experience PONV. In this study, we investigated whether the Y129S and -100_-102AAG deletion polymorphisms of the 5-HT3B receptor gene affect the efficacy of ondansetron in preventing PONV. MATERIALS AND METHODS: Two hundred and forty-five adult patients who underwent laparoscopic cholecystectomy were enrolled. Ondansetron 0.1 mg/kg was intravenously administered 30 minutes before the end of surgery. Genomic DNA was prepared from blood samples using a nucleic acid isolation device. Both the Y129S variant and the -100_-102AAG deletion variant were screened for using a single base primer extension assay and a DNA direct sequencing method, respectively. The relationship between genetic polymorphisms and clinical outcomes of ondansetron treatment was investigated. RESULTS: Among the 5-HT3B AAG deletion genotypes, the incidence of PONV was higher in patients with the homomutant than with other genotypes during the first 2 hours after surgery (p=0.02). There were no significant differences in the incidence of PONV among genotypes at 2-24 hours after surgery. In the Y129S variants of the 5-HT3B receptor gene, there were no significant differences in the incidence of PONV among genotypes during the first 2 hours and at 2-24 hours after surgery. CONCLUSION: The response to ondansetron for PONV was significantly influenced by the -100_-102AAG deletion polymorphisms of the 5-HT3B gene. Thus, the -100_-102AAG deletion variants may be a pharmacogenetic predictor for responsiveness to ondansetron for PONV.

Ondansetron versus Amitriptyline in the Treatment of Peripheral Neuropathy: A Randomized Double Blind Prospective Clinical Study.

Background and Objective: Clinical trials have shown the potential use of 5-HT3 receptor antagonists like Ondansetron, Tropisetron and Zacopride in a number of disorders of gastrointestinal tract and the central nervous system such as cancer chemotherapy induced vomiting, anxiety, depression, schizophrenia and migraine. Various experimental and clinical studies also point the usefulness of Ondansetron in neuropathic pain. Therefore, the present study was conducted to find out whether Ondansetron could be used as an alternative to a standard drug, Amitriptyline in the treatment of peripheral neuropathy. Methodology: A randomized double blind prospective clinical study was conducted on Original Research Article British Journal of Medicine & Medical Research, 4(26): 4444-4454, 2014 4445 thirty six patients of peripheral neuropathy divided into two groups of equal number of patients. Group 1 received Ondansetron 8 mg per day while Group 2 received Amitriptyline 25 mg per day. Patients were being evaluated on the basis of improvements (decrease) in LANSS (Leeds Assessment of Neuropathic Symptoms and Signs), VAS (Visual Analogue Scale) and NCV (Nerve Conduction Velocity) for six weeks. Student’s ttest and/or repeated measure ANOVA followed by Bonferoni correlation was used to compare sets of paired observations. The Friedman test followed by multiple comparisons was used to compare the data which was not normally distributed. Results: LANSS and VAS scores showed significant improvements in the 1st and 2nd visit in both the groups. NCV showed improvement in Ondansetron group with less number of adverse effects compared to that of Amitriptyline. NCV in Amitriptyline group demonstrated significant increase in one of the parameters, F-waves, indicating a worsening in left tibial nerve (p=0.036), whereas no such change was found in the group treated with Ondansetron. Conclusion: Ondansetron has beneficial role in peripheral neuropathy by improving its sensory component as it significantly decreased LANSS and VAS scores. Our results also demonstrated that Ondansetron was at least as efficacious as Amitriptyline in the treatment of peripheral neuropathy with lesser adverse effects.