Identification and molecular study on the interaction of Schisandrin C with human 5-HT3A receptor.

Schisandrin C (Sch C) is one of the main components of Schisandra chinensis (Schisandra). Since the olden times, Schisandra has been used as a traditional herbal medicine in Asia. Recent studies have shown that Schisandra is effective against irritable bowel syndrome (IBS) in an animal model and affects IBS through the 5-HT3A pathway in the IBS rat model. However, there lacks fundamental research on the interaction of specific components of Schisandra with the 5-HT3A receptor for the treatment of IBS. We hypothesized that a component of Schisandra binds to the 5-HT3A receptor and identified Sch C via a screening work using two electrode-voltage clamps (TEVC). Thus, we aimed to elucidate the neuropharmacological actions between Sch C and the 5-HT3A receptor at molecular and cellular levels. Co-treatment of Sch C with 5-HT inhibited I5-HT in a reversible, concentrate-dependent, like-competition, and voltage-independent manner, and IC50 values of Sch C. Besides, the main binding positions of Sch C were identified through 3D modeling and point mutation were V225A and V288Y on 5-HT3A receptor. Thus, we suggest the potential of Sch C in treating IBS in a manner that suppresses excessive neuronal serotonin signaling in the synapse of sensory neurons and enterochromaffin (EC) cells. In conclusion, the results demonstrate the mechanism of interaction between Sch C and 5-HT3A receptor and reveal Sch C as a novel antagonist.

Efficacy and Safety of Serotonin Receptor Ligands in the Treatment of Irritable Bowel Syndrome: A Review.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic, recurrent bowel disorder with an unknown etiology, which is most likely multifactorial. Increased mucosal permeability, visceral hypersensitivity and activation status of intestinal mucosal immune cells cause changes in gastrointestinal (GI) motility, secretion and sensation observed in the course of IBS. Permanent, cumbersome symptoms, such as diarrhea, constipation and abdominal pain greatly lower the quality of life of IBS patients. On this basis, according to the Rome IV criteria, different forms of IBS can be distinguished. OBJECTIVE: This article focuses on the role of serotonin system in the pathophysiology of IBS as a potential therapeutic target. We shortly describe several molecules, associated with serotonin receptors, mainly 5-HT3 receptor antagonists and 5-HT4 receptor agonists, that are used in the treatment of motility disorders and visceral pain in IBS patients. We summarize the findings obtained in the clinical trials and elaborate on the safety of the serotonin ligands. Although the majority of serotonin receptor ligands relieve global symptoms, there are also some adverse effects, which can be dangerous for patients. RESULTS AND CONCLUSION: We postulate that currently, among all serotonin-targeting compounds, ramosetron is the best treatment option for IBS-D patients, due to its exceptional efficacy in both genders as well as good tolerability. Whereas, tegaserod is highly recommended for IBS-C sufferers. Nevertheless, numerous studies on the new serotonin receptor ligands are conducted to ensure the delivery of novel compounds with improved efficacy and safety profiles.

Prevention of gastrointestinal side-effects in paediatric oncology: what are the guidelines?

PURPOSE OF REVIEW: Gastrointestinal side-effects, particularly with regard to alimentary tract mucositis and chemotherapy-induced nausea and vomiting (CINV), continue to be frequent and debilitating symptomatic conditions among children and adolescents receiving cytotoxic cancer therapy. Further avenues of progress for mucositis and CINV prevention in paediatric oncology setting are warranted. RECENT FINDINGS: The current article reviews the major guidelines and literature published in 2016 pertaining to the prevention of mucositis and CINV. Considerable professional organizational efforts have been made to develop consensus-based or evidence-based guidelines that periodically update to define basic standards of mucositis and CINV prevention. There are a few published works in 2016 that may contribute to the emerging evidence on prevention of mucositis and CINV in the paediatric setting for future guideline updates. SUMMARY: The concomitant use of 5-HT3 receptor antagonist and dexamethasone are effective to prevent acute and delayed CINV in children who are to receive highly or moderately emetogenic chemotherapy. Optimal control of acute and delayed CINV can prevent anticipatory CINV. Oral care protocols would be beneficial to prevent mucositis in children across all cancer treatment modalities. Cryotherapy or low-level light therapy may be applied to cooperative children undergoing chemotherapy or haematological stem cell transplant conditioning regimens with a high rate of mucositis.

Dietary and pharmacological treatment of abdominal pain in IBS.

This review introduces the principles of visceral sensation and appraises the current approaches to management of visceral pain in functional GI diseases, principally IBS. These approaches include dietary measures including fibre supplementation, low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and pharmacological approaches such as antispasmodics, peppermint oil, antidepressants (tricyclic agents, selective serotonin reuptake inhibitors), 5-HT3 receptor antagonists (alosetron, ondansetron, ramosetron), non-absorbed antibiotic (rifaximin), secretagogues (lubiprostone, linaclotide), µ-opioid receptor (OR) and κ-OR agonist, δ-OR antagonist (eluxadoline), histamine H1 receptor antagonist (ebastine), neurokinin-2 receptor antagonist (ibodutant) and GABAergic agents (gabapentin and pregabalin). Efficacy and safety are discussed based on pivotal trials or published systematic reviews and meta-analysis, expressing ORs or relative risks and their 95% CIs. Potential new approaches may be based on recent insights on mucosal expression of genes, and microRNA and epigenetic markers in human biopsies and in animal models of visceral hypersensitivity.The objectives of this review are to appraise the physiology and anatomy of gut sensation and the efficacy in the relief of visceral pain (typically in IBS) of several classes of therapies. These include fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and different classes of medications (box 1). Box 1Classes of pharmacological agents for visceral painAntidepressants (tricyclic agents, selective serotonin reuptake inhibitors)Peppermint oil5-HT3 receptor antagonists (alosetron, ondansetron, ramosetron)Non-absorbed antibiotic (rifaximin)Secretagogues (lubiprostone, linaclotide)µ-Opioid receptor (OR) and κ-OR agonist and δ-OR antagonist (eluxadoline)Histamine H1 receptor antagonist (ebastine)Neurokinin-2 receptor antagonist (ibodutant)GABAergic agents (gabapentin and pregabalin).

Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) on lipopolysaccharide-induced anxiety models in mice.

BACKGROUND: 5-HT3 receptor antagonists play a key role in the management of psychiatric disorders such as, depression and anxiety. They may act through modulation of serotonergic transmission. In the present study, a novel and potential 5-HT3 receptor antagonist, 6g (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone, which exhibited good log P (3.08) and pA2 (7.5) values was screened for its anxiolytic property in lipopolysaccharide (LPS) induced anxiety models. METHODS: LPS, an endotoxin, present in the cell wall of Gram negative bacteria was injected 0.83 mg/kg, i.p. as a single dose to induce anxiety-like symptoms in mice. Compound 6g (1 and 2 mg/kg, p.o.) and standard fluoxetine (FLX) (20 mg/kg, p.o.) were injected to treatment groups for 7 days and evaluated in various behavioral paradigms such as elevated plus maze (EPM), light and dark (L/D) test, and open field test (OFT). Their effects on serotonin levels in mice brain were also examined. RESULTS: The results showed that LPS induced anxiety-like symptoms in mice, as indicated by a significantly decreased percentage open arm entries and percentage time spent in open arms in EPM; decreased time spent in light area and number of transition between chambers in L/D test; decreased ambulation and rearing scores in OFT. Compound 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) reversed the LPS-induced behavioral changes and significantly affected all the behavioral parameters mentioned above. In addition 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) increased the levels of serotonin in mice brain. CONCLUSIONS: Compound 6g produced anxiolytic-like effects in various anxiety paradigms in LPS-treated mice as well as restored the decreased serotonin levels in mice brain.

Neuropharmacological and neurochemical evaluation of N-n-propyl-3-ethoxyquinoxaline-2-carboxamide (6n): a novel serotonergic 5-HT3 receptor antagonist for co-morbid antidepressant- and anxiolytic-like potential using traumatic brain injury model in rats.

BACKGROUND: Several preclinical studies have shown that serotonergic 5-HT3 receptor antagonists play an important role in the management of neuropsychiatric disorders, such as depression and anxiety. In the present study the compound "6n" (N-n-propyl-3-ethoxyquinoxaline-2-carboxamide), a novel 5-HT3 receptor antagonist with an optimal log P (2.52) and pA2 (7.6) value was screened for its neuro-pharmacological potential in chronic rodent models of depression and anxiety named traumatic brain injury (TBI). METHODS: In this model, a 1 cm midline scalp incision was made, and the muscles were retracted to expose the skull. A stainless steel disc (10 mm in diameter and 3 mm in depth) was placed centrally between the lambda and bregma regions. The injury was induced using the impact acceleration model of TBI. Specifically, a 400 g metal weight was dropped from a height of 1 m guided by a straight pipe, onto the metal disc placed over the rat's skull. RESULTS: The behavioral anomalies of the TBI rats were attenuated by the chronic treatment of compound 6n (1 and 2 mg/kg, p.o.; 14 days) as observed by the modified open field test (ambulation, rearing, and fecal pellet), sucrose consumption test (% sucrose consumption), elevated plus maze [% open arm entries [OAE] and % time spent in open arm (TSOA)], and marble burying test (numbers). In addition, 6n also increased the levels of neurotransmitters (norepinephrine and serotonin) and brain derived neurotrophic factor (BDNF) in TBI rats. CONCLUSIONS: The result suggests that compound 6n exhibited antidepressant- and anxiolytic-like effects in rodent models of depression and anxiety.

Shuyu Capsules Relieve Premenstrual Syndrome Depression by Reducing 5-HT3AR and 5-HT3BR Expression in the Rat Brain.

The effects of the Shuyu capsule on 5-HT3AR and 5-HT3BR expression in a rat model of premenstrual syndrome (PMS) depression and on 5-HT3AR and 5-HT3BR expression and hippocampal neuron 5-HT3 channel current were investigated, to elucidate its mechanism of action against PMS depression. PMS depression model rats were divided into depression and Shuyu- and fluoxetine-treated groups, which were compared to control rats for frontal lobe and hippocampal 5-HT3AR and 5-HT3BR expression and behavior. The depressed model rats displayed symptoms of depression, which were reduced in treated and normal control rats. Frontal lobe and hippocampal 5-HT3AR and 5-HT3BR levels were significantly higher in the model versus the control group and were significantly lower in the Shuyu group. As compared to control rats, the 5-HT3R channel current in the model group was significantly higher; the 5-HT3R channel current in hippocampal neurons treated with serum from Shuyu group rats was significantly lower than that in those treated with model group serum. Thus, PMS depression may be related to 5-HT3AR and 5-HT3BR expression and increased 5-HT3 channel current. Shuyu capsules rectified abnormal 5-HT3AR and 5-HT3BR expression and 5-HT3 channel current changes in a rat model; this finding may provide insight into treating PMS depression.

Management of Postembolization Syndrome Following Hepatic Transarterial Chemoembolization for Primary or Metastatic Liver Cancer.

BACKGROUND: Transarterial chemoembolization (TACE) is an established treatment in managing liver primary neoplasms or liver metastases. Postembolization syndrome (PES) is a common adverse event defined as fever without associated sepsis, pain in the right upper quadrant, and nausea and/or vomiting. OBJECTIVE: This integrative review aims to identify effective management strategies for PES or one of its characterizing symptoms (fever, pain, and nausea and/or vomiting). METHODS: Searches of electronic databases MEDLINE, EMBASE, and CINAHL were conducted. Fifteen articles were identified for inclusion. Seven addressed all symptoms of PES, and 8 studies focused on individual symptoms of PES. RESULTS: Interventions identified are intra-arterial lidocaine, oral and intravenous analgesics, steroids, wrist-ankle acupuncture, antibiotics, and 5-HT3 receptor antagonists. Findings are explicated according to individual symptoms of PES. Intra-arterial lidocaine, steroids, and a 5-HT3 receptor antagonist are found to offer potential benefit in the management of PES symptoms. CONCLUSION: A number of interventions have shown potential benefit in the management of PES. A systemic approach using combination therapy is necessary to effectively manage characterizing symptoms. Further research is needed to determine the impact of primary disease site, TACE technique, and chemotherapeutic agent on PES. IMPLICATIONS FOR PRACTICE: Oncology nurses are uniquely placed to undertake thorough patient assessment after TACE and implement early intervention to effectively manage PES.

Japanese Society of Clinical Oncology clinical practice guidelines 2010 for antiemesis in oncology: executive summary.

The purpose of this article is to disseminate the standard of antiemetic therapy for Japanese clinical oncologists. On the basis of the Appraisal of Guidelines for Research and Evaluation II instrument, which reflects evidence-based clinical practice guidelines, a working group of the Japanese Society of Clinical Oncology (JSCO) reviewed clinical practice guidelines for antiemesis and performed a systematic review of evidence-based domestic practice guidelines for antiemetic therapy in Japan. In addition, because health-insurance systems in Japan are different from those in other countries, a consensus was reached regarding standard treatments for chemotherapy that induce nausea and vomiting. Current evidence was collected by use of MEDLINE, from materials from meetings of the American Society of Clinical Oncology National Comprehensive Cancer Network, and from European Society of Medical Oncology/Multinational Association of Supportive Care in Cancer guidelines for antiemesis. Initially, 21 clinical questions (CQ) were selected on the basis of CQs from other guidelines. Patients treated with highly emetic agents should receive a serotonin (5-hydroxytryptamine; 5HT3) receptor antagonist, dexamethasone, and a neurokinin 1 receptor antagonist. For patients with moderate emetic risk, 5HT3 receptor antagonists and dexamethasone were recommended, whereas for those receiving chemotherapy with low emetic risk dexamethasone only is recommended. Patients receiving high-emetic-risk radiation therapy should also receive a 5HT3 receptor antagonist. In this paper the 2010 JSCO clinical practice guidelines for antiemesis are presented in English; they reveal high concordance of Japanese medical circumstances with other antiemetic guidelines that are similarly based on evidence.

Effect of a novel 5-HT3 receptor antagonist 4i, in corticosterone-induced depression-like behavior and oxidative stress in mice.

Stress in our daily life severely affects the normal physiology of the biological system. Dysregulation of hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the development of depression-like behavior, which remains under diagnosed and poorly treated. Exogenous corticosterone (CORT) administration has been demonstrated to develop a depression model, which has shown to mimic HPA-axis induced depression-like state in rodents. In the present study, the effect of a novel 5HT3 receptor, 4i was examined on CORT induced depression in mice. CORT (30mg/kg, subcutaneously) was given for 4-weeks to mice in control group, while mice in drug treated group were given 4i (0.5-1mg/kg, intraperitoneally)/fluoxetine (as a positive control, 10mg/kg), for the last 2-weeks of CORT dosing. Repeated CORT dosing caused depression-like behavior in mice as indicated by increased despair effects in forced swim test (FST) and anhedonia in sucrose preference test. In addition, CORT administration induced oxidative load in the brain with significant increase in pro-oxidant (lipid peroxidation and nitrite levels) markers and a substantial decline in anti-oxidant defense (catalase and reduced glutathione levels) system, indicating a direct effect of stress hormones in the induction of the brain oxidative damage. On the other hand, 4i and fluoxetine treatment reversed the CORT induced depressive-like deficits. Furthermore, 4i and fluoxetine prevented CORT induced oxidative brain insults, which may plausibly demonstrate one of the key mechanisms for antidepressant-like effects of the compounds. Thus, the study suggests that 5HT3 antagonist; 4i may be implicated as pharmacological intervention targeting depressive-like anomaly associated with HPA-axis dysregulation.

Randomized, double-blind, placebo-controlled study to investigate the pharmacodynamic interaction of 5-HT3 antagonist ondansetron and paracetamol in postoperative patients operated in an ENT department under local anesthesia.

BACKGROUND: The preclinical incision pain models and clinical studies in healthy volunteers have demonstrated the central serotonergic analgesic mechanism, paracetamol analgesia. This has been evidenced by raised serotonin concentrations in the brain following paracetamol administration in a few studies. The inhibition of paracetamol analgesia by 5-HT3 antagonists suggests that this analgesia is 5-HT3 mediated. However, in a few studies, 5-HT3 antagonists themselves exhibited an analgesic action. Various studies in this context stated intricate results. The present study was intended to understand the pharmacodynamic interaction between paracetamol and ondansetron in postoperative patients. METHODS: This randomized clinical trial included 32 postoperative cases of either sex, ages between 18 and 70 years. The patients were randomly allocated into the placebo and test groups and received respective treatment at the end of surgery. The pain score was recorded using Visual Analogue Scale (VAS) and Face, Legs, Activity, Cry, Consolability (FLACC) behavioral scale at awakening and every 30 min for the next 3 h. The postoperative rescue analgesic consumption for 24 h was recorded. The data were analyzed using OpenEpi and SciStatCalc statistical software. RESULTS: A significantly higher pain score was observed in the placebo group postoperatively for 60 min on VAS (p<0.05 and p<0.01), whereas the FLACC behavior scale score was significantly higher at 120 and 150 min (p<0.05). The test group patients were more comfortable throughout the study, and the postoperative analgesic requirement was significantly lesser (p<0.05). CONCLUSIONS: The pharmacodynamic interaction between paracetamol and ondansetron coadministration does not block but instead increase paracetamol analgesia, reduce the postoperative analgesic requirement, and improve the postoperative comfort level.

Phase II study on EANI combined with hydrochloride palonosetron for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy.

OBJECTIVE: To investigate the electronic anti-nausea instrument (EANI) combined with hydrochloride palonosetron for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. METHODS: Patients who received highly emetogenic chemotherapy were randomly assigned to a treatment group (60 patients) treated with EANI combined with hydrochloride palonosetron, and control group (also 60 patients) given only hydrochloride palonosetron. Chemotherapy related nausea and vomiting were observed and recorded in both groups of patients from the start till the end of chemotherapy. RESULTS: Complete control rates of vomiting in treatment and control group were 40%, and 35%, respectively, without any statistical ly significant difference (p> 0.05); however the response rates are 95.0%, 78.3%, respectively, with statistical difference (p< 0.05). Complete control rates of nausea in treatment and control group were 36.7%, 30%, respectively, without statistical difference (p> 0.05); but the response rates are 90.0%, 76.7%, respectively, with statistical difference (p<0.05). CONCLUSION: EANI combined with hydrochloride palonosetron for prevention of nausea and vomiting induced by chemotherapy could be more effective than hydrochloride palonosetron alone, and can be recommended for use in prevention and treatment of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy.

Management of chemotherapy-induced nausea and vomiting : focus on newer agents and new uses for older agents.

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a serotonin 5-HT3 receptor antagonist, dexamethasone and a neurokinin 1 (NK1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second-generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity and a different mechanism of action than the first-generation 5-HT3 receptor antagonists appears to be the most effective agent in its class. Aprepitant, the first and only agent clinically available in the NK1 receptor antagonist drug class has been used effectively as an additive agent to the 5-HT3 receptor antagonists and dexamethasone to control CINV. Rolapitant and netupitant are other NK1 receptor antagonists that are currently in phase III clinical trials. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a US-FDA approved antipsychotic, has emerged in recent trials as an effective preventative agent for CINV, as well as a very effective agent for the treatment of breakthrough emesis and nausea. Clinical trials using gabapentin, cannabinoids and ginger have not been definitive regarding their efficacy in the prevention of CINV. Additional studies are necessary for the control of nausea and for the control of CINV in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.

Ginger (Zingiber officinale) reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients.

PURPOSE: Despite the widespread use of antiemetics, nausea continues to be reported by over 70% of patients receiving chemotherapy. METHODS: In this double blind, multicenter trial, we randomly assigned 744 cancer patients to four arms: 1) placebo, 2) 0.5 g ginger, 3) 1.0 g ginger, or 4) 1.5 g ginger. Nausea occurrence and severity were assessed at a baseline cycle and the two following cycles during which patients were taking their assigned study medication. All patients received a 5-HT(3) receptor antagonist antiemetic on Day 1 of all cycles. Patients took three capsules of ginger (250 mg) or placebo twice daily for 6 days starting 3 days before the first day of chemotherapy. Patients reported the severity of nausea on a 7-point rating scale ("1" = "Not at all Nauseated" and "7" = "Extremely Nauseated") for Days 1-4 of each cycle. The primary outcomes were to determine the dose and efficacy of ginger at reducing the severity of chemotherapy-induced nausea on Day 1 of chemotherapy. RESULTS: A total of 576 patients were included in final analysis (91% female, mean age = 53). Mixed model analyses demonstrated that all doses of ginger significantly reduced acute nausea severity compared to placebo on Day 1 of chemotherapy (p = 0.003). The largest reduction in nausea intensity occurred with 0.5 g and 1.0 g of ginger (p = 0.017 and p = 0.036, respectively). Anticipatory nausea was a key factor in acute chemotherapy-induced nausea (p < 0.0001). CONCLUSIONS: Ginger supplementation at a daily dose of 0.5 g-1.0 g significantly aids in reduction of the severity of acute chemotherapy-induced nausea in adult cancer patients.

Clinical roundtable monograph. Treatment of chemotherapy-induced nausea and vomiting: a post-MASCC 2010 discussion.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and troubling side effects of treatment, and the side effect cancer patients tend to fear most. An improved understanding of the pathophysiology underlying CINV, together with a clear definition of the risk for nausea and vomiting associated with specific chemotherapeutic agents, has for allowed the development of specific and effective antiemetic regimens. Anti­emesis is most effective when used prophylactically, a principle shared among CINV management guidelines. Several antiemetic drug classes are available; among the most effective of these are serotonin (5HT3) receptor antagonists, neurokinin 1 (NK1) receptor antagonists, and steroids (primarily dexamethasone), although others are commonly used as well. When choosing an appropriate antiemetic regimen, clinicians should consider patient-specific factors such as sex and prior history of CINV, as well as treatment-specific factors such as the emetogenic potential of each chemotherapeutic agent. Using these factors, clinicians can follow the available algorithms included in guidelines from groups such as the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the Multinational Association for Supportive Care in Cancer. Ongoing and future clinical trials will be pivotal in helping to further delineate the optimal strategies to prevent and manage CINV in cancer patients.

A review of granisetron, 5-hydroxytryptamine3 receptor antagonists, and other antiemetics.

Nausea and vomiting are 2 of the most upsetting adverse reactions of chemotherapy. Current guidelines propose 5-hydroxytryptamine3 (5-HT3) receptor antagonists as a pharmacologic intervention for acute and delayed nausea and vomiting [chemotherapy-induced nausea and vomiting (CINV)] associated with moderately and highly emetogenic chemotherapy. Meanwhile, both postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting are challenging situations after surgeries and procedures. Prophylactic and therapeutic combinations of antiemetics are recommended in patients at high risk of suffering from PONV and postdischarge nausea and vomiting. Granisetron (Kytril) is a selective 5-HT3 receptor antagonist that does not induce or inhibit the hepatic cytochrome P-450 system in vitro. There are also 4 other antagonists of 5-HT3 receptor (dolasetron, ondansetron, palonosetron, and tropisetron) being metabolized via the CYP2D6 and are subject to potential genetic polymorphism. The launch of a new class of antiemetics, the substance P/neurokinin1 receptor antagonists, was attributed to the scientific update on the central generator responsible for emesis and role of substance P. There has been mounting interest in exploring integrative medicine, either acupuncture or acustimulation of P6 (Nei-Kuwan), to complement the western medicine for prevention and management of nausea and vomiting. The potential application of cannabinoids, either alone or in combination with other agents of different mechanism, could contribute further to improve outcome in CINV. Implementation of future treatment guidelines for more effective management of CINV and PONV could certainly improve the efficacy and outcome of cancer and postoperative care.