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John A. Rudd - One of the best experts on this subject based on the ideXlab platform.
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action of bacopa monnieri to antagonize cisplatin Induced Emesis in suncus murinus house musk shrew
Journal of Pharmacological Sciences, 2017Co-Authors: Ihsan Ullah, Zengbing Lu, Sze Wa Chan, Fazal Subhan, John A. RuddAbstract:Abstract Bacopa monnieri ( BM , family Scrophulariaceae) is used in several traditional systems of medicine for the management of epilepsy, depression, neuropathic pain, sleep disorders and memory deficits. The present study investigated the potential of BM methanol ( BM -MetFr) and BM n -butanol fractions ( BM -ButFr) to reduce Chemotherapy-Induced Emesis in Suncus murinus (house musk shrew). Cisplatin (30 mg/kg, i.p.) reliably Induced retching and/or vomiting over a 2 day period. BM -MetFr (10–40 mg/kg, s.c.) and BM -ButFr (5–20 mg/kg, s.c.) antagonized the retching and/or vomiting response by ∼59.4% ( p p 3 receptor antagonist, palonosetron (0.5 mg/kg, s.c.), reduced the response by ∼71% ( p N -(2-mercaptopropionyl)-glycine (30–300 mg/kg, s.c.) reduced the retching and/or vomiting response occurring on day one non-significantly by 44% ( p > 0.05). In conclusion, the n -butanol fractions of BM have anti-emetic activity comparable with palonosetron and MPG. BM may be useful alone or in combination with other anti-emetic drugs for the treatment of Chemotherapy-Induced Emesis in man.
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action of bacopa monnieri to antagonize cisplatin Induced Emesis in suncus murinus house musk shrew
Journal of Pharmacological Sciences, 2017Co-Authors: Ihsan Ullah, Sze Wa Chan, Fazal Subhan, John A. RuddAbstract:Abstract Bacopa monnieri (BM, family Scrophulariaceae) is used in several traditional systems of medicine for the management of epilepsy, depression, neuropathic pain, sleep disorders and memory deficits. The present study investigated the potential of BM methanol (BM-MetFr) and BM n-butanol fractions (BM-ButFr) to reduce Chemotherapy-Induced Emesis in Suncus murinus (house musk shrew). Cisplatin (30 mg/kg, i.p.) reliably Induced retching and/or vomiting over a 2 day period. BM-MetFr (10–40 mg/kg, s.c.) and BM-ButFr (5–20 mg/kg, s.c.) antagonized the retching and/or vomiting response by ∼59.4% (p 0.05). In conclusion, the n-butanol fractions of BM have anti-emetic activity comparable with palonosetron and MPG. BM may be useful alone or in combination with other anti-emetic drugs for the treatment of Chemotherapy-Induced Emesis in man.
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Action of Bacopa monnieri to antagonize cisplatin-Induced Emesis in Suncus murinus (house musk shrew)
Elsevier, 2017Co-Authors: Ihsan Ullah, Sze Wa Chan, Fazal Subhan, John A. RuddAbstract:Bacopa monnieri (BM, family Scrophulariaceae) is used in several traditional systems of medicine for the management of epilepsy, depression, neuropathic pain, sleep disorders and memory deficits. The present study investigated the potential of BM methanol (BM-MetFr) and BM n-butanol fractions (BM-ButFr) to reduce Chemotherapy-Induced Emesis in Suncus murinus (house musk shrew). Cisplatin (30 mg/kg, i.p.) reliably Induced retching and/or vomiting over a 2 day period. BM-MetFr (10–40 mg/kg, s.c.) and BM-ButFr (5–20 mg/kg, s.c.) antagonized the retching and/or vomiting response by ∼59.4% (p
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the differential antiemetic properties of glp 1 receptor antagonist exendin 9 39 in suncus murinus house musk shrew
Neuropharmacology, 2014Co-Authors: Sze Wa Chan, Zengbing Lu, Chi Kong Yeung, John A. RuddAbstract:Abstract The use of glucagon-like peptide-1 (7–36) amide (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus is commonly associated with nausea and vomiting. Previous studies using Suncus murinus revealed that the GLP-1 receptor agonist, exendin-4, induces Emesis via the brainstem and/or hypothalamus. The present study investigated the mechanism of exendin-4-Induced Emesis in more detail. Ondansetron (1 mg/kg, s.c.) and CP-99,994 (10 mg/kg, s.c) failed to reduce Emesis Induced by exendin-4 (3 nmol, i.c.v.), suggesting that 5-HT3 and NK1 receptors are not involved in the mechanism. In other studies, the GLP-1 receptor antagonist, exendin (9–39), antagonised Emesis and c-Fos expression in the brainstem and the paraventricular hypothalamus Induced by the chemotherapeutic drug cisplatin (30 mg/kg, i.p.; p 0.05), or copper sulphate pentahydrate (120 mg/kg, p.o.; p > 0.05). GLP-1 receptors may therefore represent a potential target for drugs to prevent Chemotherapy-Induced Emesis in situations where 5-HT3 and NK1 receptor antagonists fail.
Paul J Hesketh - One of the best experts on this subject based on the ideXlab platform.
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novel neurokinin 1 antagonists as antiemetics for the treatment of Chemotherapy Induced Emesis
Supportive Cancer Therapy, 2006Co-Authors: Kesava G Reddy, Richard J Gralla, Paul J HeskethAbstract:Abstract Despite significant advances in supportive care in oncology, many patients with cancer still experience Chemotherapy-Induced nausea and vomiting (CINV). Historically, there were only 3 neurotransmitter receptors (dopamine D2, cannabinoid- 1, and 5-hydroxytryptamine-3) that were the known targets for antiemetic therapy. Major advances in the management of Chemotherapy-Induced Emesis were seen with the introduction of 5-hydroxytryptamine-3 receptor antagonists, which include palonosetron, ondansetron, tropisetron, dolasetron, and granisetron. However, recently, selective inhibitors of substance P have shown promising activity in the management of CINV in patients with cancer. Substance P mediates a number of biologic effects by binding to a specific neuroreceptor, neurokinin-1 (NK-1). Among the NK-1 receptor antagonists, aprepitant has been approved for the treatment of CINV. Currently, several other NK-1 receptor antagonists, including casopitant, vestipitant, netupitant, and SCH619734, are undergoing clinical evaluation for the prevention of CINV in patients with a variety of malignancies. The clinical potential of these novel NK-1 receptor antagonists and their respective ongoing clinical trials for the management of Chemotherapy-Induced Emesis are discussed briefly herein.
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differential involvement of neurotransmitters through the time course of cisplatin Induced Emesis as revealed by therapy with specific receptor antagonists
European Journal of Cancer, 2003Co-Authors: Paul J Hesketh, S Van Belle, Matti Aapro, F Tattersall, R Naylor, Richard Hargreaves, Alexandra D Carides, Judith K Evans, Kevin J HorganAbstract:Advances in antiemetic therapy for Chemotherapy-Induced Emesis have resulted in improved protection against symptoms occurring within 24 h of Chemotherapy. However, the vomiting which tends to occur beyond 24 h after Chemotherapy (delayed-phase vomiting) is still relatively poorly controlled by the currently available drugs, suggesting that more than one mechanism may mediate these symptoms. The standard antiemetic regimen currently recommended for prevention of Chemotherapy-Induced Emesis includes a serotonin (5-HT3) antagonist and a corticosteroid. The neurokinin-1 (NK1) antagonist aprepitant represents a new class of antiemetic currently in clinical development. Using data obtained in 2 Phase II clinical trials of aprepitant in patients receiving Chemotherapy based on the highly emetogenic chemotherapeutic agent cisplatin, we compared the time course of antiemetic effect of aprepitant, a 5-HT3 antagonist, or a combination of both. Over the entire observation period (up to 7 days post-cisplatin), patients who received the NK1 antagonist had a superior prevention of Emesis. However, in the first 24 h after cisplatin, Emesis occurred in fewer patients who received the 5-HT3 antagonist than in patients who did not receive this class of drug. Furthermore, the majority of treatment failures in patients who received the NK1 antagonist occurred within the first 8–12 h of Chemotherapy, whereas the treatment failures in patients who received a 5-HT3 antagonist were more evenly distributed over time. Patients who received both drugs had superior control of symptoms compared with patients who received one or the other. The difference in the time course of Emesis blockade observed with two different classes of receptor antagonists provides substantial evidence for involvement of separate pathophysiological mechanisms in Chemotherapy-Induced vomiting. Serotonin mediates the early vomiting process that occurs within 8–12 h following cisplatin-based Chemotherapy, after which time substance P acting at NK1 receptors becomes the dominant mediator of vomiting
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drug treatment of Chemotherapy Induced delayed Emesis
Drugs, 1996Co-Authors: Ranjana Tavorath, Paul J HeskethAbstract:Chemotherapy-Induced Emesis has a major adverse impact on patients undergoing therapy for various malignancies, and this has led to considerable research in this field. Most investigative efforts have concentrated on the acute phase of Emesis that occurs within the first 24 hours after Chemotherapy, and significant strides forward have been made with this problem. Better control of acute Emesis with newer agents such as the serotonin 5-HT3 receptor antagonists has focused increasing attention on a second phase of nausea and vomiting, known as delayed Emesis, which occurs more than 24 hours after Chemotherapy. This delayed phase is often not as well controlled with the antiemetics that have proven effective in acute Emesis, and contributes to the distress associated with emetogenic Chemotherapy.
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treatment of Chemotherapy Induced Emesis in the 1990s impact of the 5 ht3 receptor antagonists
Supportive Care in Cancer, 1994Co-Authors: Paul J HeskethAbstract:Considerable progress has been made in the development of means to limit nausea and vomiting arising from cancer Chemotherapy. A number of key conceptual advances in the last decade have been critically important. These include recognition of the value of combination antiemetic therapy, identification of important patient- and treatment-related factors predictive of Emesis, and appreciation of the importance of serotonin (5-HT) in the pathophysiology of Emesis and the value of selective antagonists of the type-3 serotonin receptor. Comparative trials of the 5-HT3 receptor antagonists and classic antiemetic agents have helped define optimal antiemetic approaches in a number of settings. A combination of a 5-HT3 antagonist and dexamethasone is the treatment of choice for patients receiving single- and multiple-day cisplatin. The 5-HT3 antagonists are also effective agents with noncisplatin Chemotherapy. Clear-cut superiority to classic antiemetics such as dexamethasone has not been consistently demonstrated, however. Results with the 5-HT3 antagonists in cisplatin-Induced delayed Emesis have been disappointing to date. The results of ongoing prospective trials should define their role more clearly. At present a combination of metoclopramide and dexamethasone is the treatment of choice in this setting. Results of trials comparing 5-HT3 antagonists are beginning to emerge. Available information suggests no clinically relevant differences in antiemetic efficacy between these agents. Many questions regarding the optimal use of the 5-HT3 antagonists and their integration into clinical practice remain unanswered and are the appropriate focus for additional study.
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control of Chemotherapy Induced Emesis
The New England Journal of Medicine, 1993Co-Authors: Steven M. Grunberg, Paul J HeskethAbstract:The development of antiemetic drugs has been one of the most rewarding areas of oncologic research, since therapeutic advances in this area can result in immediate improvement in the quality of life for patients undergoing Chemotherapy. Antiemetic therapy has progressed dramatically during the past decade and a half. Fifteen years ago, patients receiving cisplatin for the first time had a median of 12 vomiting episodes within the first 24 hours, whereas now more than 50 percent of such patients have no vomiting episodes at all. Theoretical and clinical challenges remain, however, in the effort to control Chemotherapy-Induced Emesis. The mechanisms of anticipatory vomiting and delayed vomiting are still not understood, and consistently effective therapeutic approaches to these problems have yet to be developed.
Charles C Horn - One of the best experts on this subject based on the ideXlab platform.
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estimation of body surface area in the musk shrew suncus murinus a small animal for testing Chemotherapy Induced Emesis
Laboratory Animals, 2017Co-Authors: Julie L Eiseman, Michael Sciullo, Hong Wang, Jan H Beumer, Charles C HornAbstract:Several cancer chemotherapies cause nausea and vomiting, which can be dose-limiting. Musk shrews are used as preclinical models for Chemotherapy-Induced Emesis and for antiemetic effectiveness. Unlike rats and mice, shrews possess a vomiting reflex and demonstrate an emetic profile similar to humans, including acute and delayed phases. As with most animals, dosing of shrews is based on body weight, while translation of such doses to clinically equivalent exposure requires doses based on body surface area. In the current study body surface area in musk shrews was directly assessed to determine the Meeh constant (Km) conversion factor (female = 9.97, male = 9.10), allowing estimation of body surface area based on body weight. These parameters can be used to determine dosing strategies for shrew studies that model human drug exposures, particularly for investigating the emetic liability of cancer chemotherapeutic agents.
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behavioral patterns associated with Chemotherapy Induced Emesis a potential signature for nausea in musk shrews
Frontiers in Neuroscience, 2011Co-Authors: Charles C Horn, Severine Henry, Kelly Meyers, Magnus S MagnussonAbstract:Nausea and vomiting are common symptoms in patients with many diseases, including cancer and its treatments. Although the neurological basis of vomiting is reasonably well known, an understanding of the physiology of nausea is lacking. The primary barrier to mechanistic research on the nausea system is the lack of an animal model. Indeed investigating the effects of anti-nausea drugs in preclinical models is difficult because the primary readout is often Emesis. It is known that animals show a behavioral profile of sickness, associated with reduced feeding and movement, and possibly these general measures are signs of nausea. Studies attempting to relate the occurrence of additional behaviors to Emesis have produced mixed results. Here we applied a statistical method, t-pattern (temporal pattern) analysis, to determine patterns of behavior associated with Emesis. Musk shrews were injected with the Chemotherapy agent cisplatin (a gold standard in Emesis research) to induce acute ( 24 h) Emesis. Emesis and other behaviors were coded and tracked from video files. T-pattern analysis revealed hundreds of non-random patterns of behavior associated with Emesis, including sniffing, changes in body contraction, and locomotion. There was little evidence that locomotion was inhibited by the occurrence of Emesis. Eating and drinking, and other larger body movements including rearing, grooming, and body rotation, were significantly less common in Emesis-related behavioral patterns in real versus randomized data. These results lend preliminary evidence for the expression of Emesis-related behavioral patterns, including reduced ingestive behavior, grooming and exploratory behaviors. In summary, this statistical approach to behavioral analysis in a pre-clinical Emesis research model could be used to assess the more global effects and limitations of drugs used to control nausea and its potential correlates, including reduced feeding and activity levels.
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computerized detection and analysis of cancer Chemotherapy Induced Emesis in a small animal model musk shrew
Journal of Neuroscience Methods, 2011Co-Authors: Dong Huang, Kelly Meyers, Severine Henry, Fernando De La Torre, Charles C HornAbstract:Vomiting is a common side effect of cancer Chemotherapy and many drug treatments and diseases. In animal studies, the measurement of vomiting usually requires direct observation, which is time consuming and often lacks temporal precision. Musk shrews have been used to study the neurobiology of Emesis and have a rapid emetic episode (∼1 s for a sequence of retching and expulsion). The aim of the current study was to develop a method to automatically detect and characterize emetic episodes Induced by the cancer Chemotherapy agent cisplatin. The body contour in each video frame was tracked and normalized to a parameterized shape basis. The tracked shape was projected to a feature space that maximized the shape variations in the consecutive frames during retching. The resulting one dimensional projection was sufficient to detect most emetic episodes in the acute (peak at 2h) and delayed (peak at 54 h) phases after cisplatin treatment. Emetic episodes were relatively invariant in the number of retches (∼6.2), duration (∼1.2s), inter-retch interval (∼198 ms), and amplitude during the 72 h after cisplatin treatment. This approach should open a new vista into Emesis research to permit tracking and analysis of Emesis in a small animal model and facilitate the development of new antiemetic therapies. These results also yield a better understanding of the brain's central pattern generator for Emesis and indicate that the retching response in the musk shrew (at ∼5.4 Hz) is the fastest ever recorded in a free-moving animal.
Lisa A. Sanchez - One of the best experts on this subject based on the ideXlab platform.
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Stratified Administration of Serotonin 5-HT_3 Receptor Antagonists (Setrons) for Chemotherapy-Induced Emesis
PharmacoEconomics, 2000Co-Authors: Lisa A. Sanchez, Mark Holdsworth, Sylvia B. BartelAbstract:The serotonin 5-HT3 receptor antagonists or ‘setrons’ have become the standard of care for the prevention of Chemotherapy-Induced Emesis (CIE) and are first-line therapy for acute CIE in healthcare organisations worldwide. However, their superior efficacy versus standard antiemetics comes at a significant cost. Currently, 3 agents are available in the US: ondansetron, granisetron and dolasetron. The most important treatment-related factor contributing to CIE is the emetogenicity of Chemotherapy. The ability to customise, or stratify, the setron dose to match the emetogenic challenge of the Chemotherapy administered has potential benefits, both clinically and economically. In adults, there is an appreciable amount of clinical literature addressing stratified administration; however, the amount of ‘hard’ economic data is rather limited. Intuitively, if clinical outcomes are equivalent, then stratified administration should be associated with economic benefits, as it generally promotes the use of doses lower than those recommended by the manufacturer. The literature strongly substantiates this for ondansetron, but is not as favourable for granisetron or dolasetron. As the rationale and justification for dose stratification is contained in the clinical literature, the authors have reviewed the pertinent literature supporting the clinical and economic benefits of dose stratification in both adult and paediatric patients. The authors also provide a discussion of various additional strategies that can be employed to ensure the appropriate and cost-effective use of setrons in real-world practice settings. These strategies include the use of lower doses than recommended by manufacturers, use for acute versus delayed phase Emesis, enhancing the antiemetic efficacy by the addition of a corticosteroid, use of oral versus injectable formulations (when appropriate) and the implementation and use of local, national and international drug use guidelines.
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stratified administration of serotonin 5 ht3 receptor antagonists setrons for Chemotherapy Induced Emesis economic implications
PharmacoEconomics, 2000Co-Authors: Lisa A. Sanchez, Mark T Holdsworth, Sylvia BartelAbstract:The serotonin 5-HT3 receptor antagonists or `setrons' have become the standard of care for the prevention of Chemotherapy-Induced Emesis (CIE) and are first-line therapy for acute CIE in healthcare organisations worldwide. However, their superior efficacy versus standard antiemetics comes at a significant cost. Currently, 3 agents are available in the US: ondansetron, granisetron and dolasetron. The most important treatment-related factor contributing to CIE is the emetogenicity of Chemotherapy. The ability to customise, or stratify, the setron dose to match the emetogenic challenge of the Chemotherapy administered has potential benefits, both clinically and economically. In adults, there is an appreciable amount of clinical literature addressing stratified administration; however, the amount of `hard' economic data is rather limited. Intuitively, if clinical outcomes are equivalent, then stratified administration should be associated with economic benefits, as it generally promotes the use of doses lower than those recommended by the manufacturer. The literature strongly substantiates this for ondansetron, but is not as favourable for granisetron or dolasetron. As the rationale and justification for dose stratification is contained in the clinical literature, the authors have reviewed the pertinent literature supporting the clinical and economic benefits of dose stratification in both adult and paediatric patients. The authors also provide a discussion of various additional strategies that can be employed to ensure the appropriate and cost-effective use of setrons in real-world practice settings. These strategies include the use of lower doses than recommended by manufacturers, use for acute versus delayed phase Emesis, enhancing the antiemetic efficacy by the addition of a corticosteroid, use of oral versus injectable formulations (when appropriate) and the implementation and use of local, national and international drug use guidelines.
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Stratified Administration of Serotonin 5-HT3 Receptor Antagonists (Setrons) for Chemotherapy-Induced Emesis: Economic Implications
1Co-Authors: Lisa A. Sanchez, Mark Holdsworth, Sylvia B. BartelAbstract:The serotonin 5-HT3 receptor antagonists or `setrons' have become the standard of care for the prevention of Chemotherapy-Induced Emesis (CIE) and are first-line therapy for acute CIE in healthcare organisations worldwide. However, their superior efficacy versus standard antiemetics comes at a significant cost. Currently, 3 agents are available in the US: ondansetron, granisetron and dolasetron. The most important treatment-related factor contributing to CIE is the emetogenicity of Chemotherapy. The ability to customise, or stratify, the setron dose to match the emetogenic challenge of the Chemotherapy administered has potential benefits, both clinically and economically. In adults, there is an appreciable amount of clinical literature addressing stratified administration; however, the amount of `hard' economic data is rather limited. Intuitively, if clinical outcomes are equivalent, then stratified administration should be associated with economic benefits, as it generally promotes the use of doses lower than those recommended by the manufacturer. The literature strongly substantiates this for ondansetron, but is not as favourable for granisetron or dolasetron. As the rationale and justification for dose stratification is contained in the clinical literature, the authors have reviewed the pertinent literature supporting the clinical and economic benefits of dose stratification in both adult and paediatric patients. The authors also provide a discussion of various additional strategies that can be employed to ensure the appropriate and cost-effective use of setrons in real-world practice settings. These strategies include the use of lower doses than recommended by manufacturers, use for acute versus delayed phase Emesis, enhancing the antiemetic efficacy by the addition of a corticosteroid, use of oral versus injectable formulations (when appropriate) and the implementation and use of local, national and international drug use guidelines.Antiemetics, Children, Corticosteroids, Cost analysis, Dolasetron, Granisetron, Guideline utilisation, Nausea, Ondansetron, Pharmacoeconomics, Serotonin 3 receptor antagonists, Vomiting
Sze Wa Chan - One of the best experts on this subject based on the ideXlab platform.
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action of bacopa monnieri to antagonize cisplatin Induced Emesis in suncus murinus house musk shrew
Journal of Pharmacological Sciences, 2017Co-Authors: Ihsan Ullah, Zengbing Lu, Sze Wa Chan, Fazal Subhan, John A. RuddAbstract:Abstract Bacopa monnieri ( BM , family Scrophulariaceae) is used in several traditional systems of medicine for the management of epilepsy, depression, neuropathic pain, sleep disorders and memory deficits. The present study investigated the potential of BM methanol ( BM -MetFr) and BM n -butanol fractions ( BM -ButFr) to reduce Chemotherapy-Induced Emesis in Suncus murinus (house musk shrew). Cisplatin (30 mg/kg, i.p.) reliably Induced retching and/or vomiting over a 2 day period. BM -MetFr (10–40 mg/kg, s.c.) and BM -ButFr (5–20 mg/kg, s.c.) antagonized the retching and/or vomiting response by ∼59.4% ( p p 3 receptor antagonist, palonosetron (0.5 mg/kg, s.c.), reduced the response by ∼71% ( p N -(2-mercaptopropionyl)-glycine (30–300 mg/kg, s.c.) reduced the retching and/or vomiting response occurring on day one non-significantly by 44% ( p > 0.05). In conclusion, the n -butanol fractions of BM have anti-emetic activity comparable with palonosetron and MPG. BM may be useful alone or in combination with other anti-emetic drugs for the treatment of Chemotherapy-Induced Emesis in man.
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action of bacopa monnieri to antagonize cisplatin Induced Emesis in suncus murinus house musk shrew
Journal of Pharmacological Sciences, 2017Co-Authors: Ihsan Ullah, Sze Wa Chan, Fazal Subhan, John A. RuddAbstract:Abstract Bacopa monnieri (BM, family Scrophulariaceae) is used in several traditional systems of medicine for the management of epilepsy, depression, neuropathic pain, sleep disorders and memory deficits. The present study investigated the potential of BM methanol (BM-MetFr) and BM n-butanol fractions (BM-ButFr) to reduce Chemotherapy-Induced Emesis in Suncus murinus (house musk shrew). Cisplatin (30 mg/kg, i.p.) reliably Induced retching and/or vomiting over a 2 day period. BM-MetFr (10–40 mg/kg, s.c.) and BM-ButFr (5–20 mg/kg, s.c.) antagonized the retching and/or vomiting response by ∼59.4% (p 0.05). In conclusion, the n-butanol fractions of BM have anti-emetic activity comparable with palonosetron and MPG. BM may be useful alone or in combination with other anti-emetic drugs for the treatment of Chemotherapy-Induced Emesis in man.
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Action of Bacopa monnieri to antagonize cisplatin-Induced Emesis in Suncus murinus (house musk shrew)
Elsevier, 2017Co-Authors: Ihsan Ullah, Sze Wa Chan, Fazal Subhan, John A. RuddAbstract:Bacopa monnieri (BM, family Scrophulariaceae) is used in several traditional systems of medicine for the management of epilepsy, depression, neuropathic pain, sleep disorders and memory deficits. The present study investigated the potential of BM methanol (BM-MetFr) and BM n-butanol fractions (BM-ButFr) to reduce Chemotherapy-Induced Emesis in Suncus murinus (house musk shrew). Cisplatin (30 mg/kg, i.p.) reliably Induced retching and/or vomiting over a 2 day period. BM-MetFr (10–40 mg/kg, s.c.) and BM-ButFr (5–20 mg/kg, s.c.) antagonized the retching and/or vomiting response by ∼59.4% (p
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the differential antiemetic properties of glp 1 receptor antagonist exendin 9 39 in suncus murinus house musk shrew
Neuropharmacology, 2014Co-Authors: Sze Wa Chan, Zengbing Lu, Chi Kong Yeung, John A. RuddAbstract:Abstract The use of glucagon-like peptide-1 (7–36) amide (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus is commonly associated with nausea and vomiting. Previous studies using Suncus murinus revealed that the GLP-1 receptor agonist, exendin-4, induces Emesis via the brainstem and/or hypothalamus. The present study investigated the mechanism of exendin-4-Induced Emesis in more detail. Ondansetron (1 mg/kg, s.c.) and CP-99,994 (10 mg/kg, s.c) failed to reduce Emesis Induced by exendin-4 (3 nmol, i.c.v.), suggesting that 5-HT3 and NK1 receptors are not involved in the mechanism. In other studies, the GLP-1 receptor antagonist, exendin (9–39), antagonised Emesis and c-Fos expression in the brainstem and the paraventricular hypothalamus Induced by the chemotherapeutic drug cisplatin (30 mg/kg, i.p.; p 0.05), or copper sulphate pentahydrate (120 mg/kg, p.o.; p > 0.05). GLP-1 receptors may therefore represent a potential target for drugs to prevent Chemotherapy-Induced Emesis in situations where 5-HT3 and NK1 receptor antagonists fail.