European Journal of Pharmacology 722 (2014) 1
Contents lists available at ScienceDirect
European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar
Preface While published literature on nausea and vomiting extends over three millennia, modern research in the area began over six decades ago. In this latter period significant advances have been made in understanding the mechanistic underpinnings of nausea and vomiting. However, basic research is still hampered by the lack of appropriate animal models that can exactly replicate the human response. While vomiting is the act of forceful removal of gastrointestinal contents, nausea is considered a subjective sensation that is more difficult to study in non-human species. In fact the act of vomiting can easily be demonstrated in vomit competent species, whereas the sensation of nausea can only be reported in the human model. Still, several surrogate behavioral markers in vomit-competent and non-competent species have been used to provide insights into the possible neurocircuitry and neurochemistry of nausea. However, caution is recommended in the interpretation of such animal findings as being relevant to the human sensation of nausea. The current volume on “new vistas in the pharmacology of nausea and vomiting” combines original and state-of-the art basic and clinical review articles to provide new insight into a patient's well-being in both the clinic and the outpatient setting. This integrated basic science and clinical compendium by leading researchers in the field of vomiting provides significant insights for the interest of not only basic scientists who are involved in deciphering mechanisms of action as well as advancing antiemetic drug development, but also to the clinicians serving diverse fields including gastroenterology, infectious diseases, oncology, general anesthesia, pain, and psychiatry, to name a few. The development of antiemetic therapy, over the years, has been largely empirical. Nonetheless, since the 1980s the ferret model of anticancer chemotherapy (cisplatin)-induced vomiting has played a pivotal role in the identification and introduction of new classes of “designer” antiemetics such as 5-HT3- and NK1-receptor antagonists for use in clinical oncology. The importance of the use of cisplatin as an emetic in ferrets in the development of 5-HT3 receptor antiemetics cannot be overstated, since prior research often utilized apomorphine as the emetogen against which such antagonists are ineffective. On the other hand, based upon its well-accepted mechanism of action, it is also difficult to comprehend why peripherally administered serotonin is an effective emetogen in the shrew but not in the ferret. To further complicate the puzzle, it has been clearly demonstrated in this volume that the L-type calcium channel antagonist nidedipine is a new class of antiemetic which has potent and broad-spectrum antiemetic efficacy in the least shrew against selective/nonselective agonists of serotonin 5HT3-, dopamine D2/3-, tachykinin NK1- and muscarinic M1-receptors. However, it fails to suppress cisplatin-induced vomiting, unless nidedipine is combined with a 5-HT3-receptor antagonist. Subsequently, the emetic/antiemetic contributions of diverse serotonergic receptors are considered, followed by separate manuscripts discussing the interaction of serotonin 5-HT3- and tachykinin NK1-receptors at the calcium level, and the role of activation of such emetic receptors on vagal neurocircuits in the regulation of nausea and vomiting. The antiemetic actions of dexamethasone are discussed next, followed by detailing the neurochemical mechanisms of (i) post-operative nausea and vomiting; (ii) opioid-induced nausea and vomiting; (iii) cyclic vomiting; and (iv) bacterial- and viral-induced emesis. Human and animal models of
0014-2999/$ - see front matter & 2013 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.ejphar.2013.12.012
nausea are considered next, followed by manuscripts detailing regulation of nausea and vomiting by cannabinoids and endocannabinoids in different emesis models, and methods to manipulate activation of cannabinoid CB1 and vanilloid TRPV1 receptors to protect against highdose cisplatin-induced vomiting in a potent manner. Thereafter, the downstream receptor signaling of cyclophosphamide-induced vomiting is compared with those of cisplatin. The potential of development of new classes of antiemetics affecting post-receptor signal transduction mechanisms is also discussed. The relevance of basic science in both the study of emesis and development of antiemetics is bridged by our clinical colleagues in the applications of available antiemetics for the prevention of nausea and vomiting due to chemotherapy (CINV) or radiation, as well as anticipatory nausea and vomiting due to CINV. The clinical utilization of the nonselective antiemetic agent olanzapine is also described followed by discussions on nausea and vomiting in advanced cancer, as well as prognostic factors for CINV. Finally, the international antiemetic therapy guidelines for the prevention of CINV are presented. I am deeply saddened to inform our colleagues and readers of the European Journal of Pharmacology that our contributing colleague Dr. Howard S. Smith passed away on May 8, 2013. At the time of his passing, Dr. Smith was an anesthesiologist and pain management specialist at Albany Medical Center. Dr. Smith wrote 90% of his current article which was completed by his colleagues. Dr. Smith has made significant contributions in the area of emesis, particularly on opioidinduced nausea and vomiting. Perhaps we could console ourselves by the wise sayings of the great Eastern poet and Philosopher Saadi of Shiraz:
Men (mankind) with good deeds never die
Dead is someone of whom no one remembers
Although we all have research and discovery imprinted in our hearts, we also do enjoy seeing patients and/or teaching the new generation of allopathic and osteopathic medical students and medical graduates for continuing medical education. As such we impart significant knowledge to them. At the end of this volume we have contributed over 40 multiple choice questions to test the knowledge of our students and colleagues in the area of nausea and vomiting. Finally, I would like to take this opportunity to thank Dr. Nijkamp for inviting me to lead this project and my co-editors Drs. John Rudd, Karen Jordan and David Warr for their excellent contributions and review of the enclosed articles by leading researchers in the field.
Professor of Pharmacology, Associate Dean Nissar A. Darmani Basic Medical Sciences and Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA
Contents lists available at ScienceDirect
European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar
Preface While published literature on nausea and vomiting extends over three millennia, modern research in the area began over six decades ago. In this latter period significant advances have been made in understanding the mechanistic underpinnings of nausea and vomiting. However, basic research is still hampered by the lack of appropriate animal models that can exactly replicate the human response. While vomiting is the act of forceful removal of gastrointestinal contents, nausea is considered a subjective sensation that is more difficult to study in non-human species. In fact the act of vomiting can easily be demonstrated in vomit competent species, whereas the sensation of nausea can only be reported in the human model. Still, several surrogate behavioral markers in vomit-competent and non-competent species have been used to provide insights into the possible neurocircuitry and neurochemistry of nausea. However, caution is recommended in the interpretation of such animal findings as being relevant to the human sensation of nausea. The current volume on “new vistas in the pharmacology of nausea and vomiting” combines original and state-of-the art basic and clinical review articles to provide new insight into a patient's well-being in both the clinic and the outpatient setting. This integrated basic science and clinical compendium by leading researchers in the field of vomiting provides significant insights for the interest of not only basic scientists who are involved in deciphering mechanisms of action as well as advancing antiemetic drug development, but also to the clinicians serving diverse fields including gastroenterology, infectious diseases, oncology, general anesthesia, pain, and psychiatry, to name a few. The development of antiemetic therapy, over the years, has been largely empirical. Nonetheless, since the 1980s the ferret model of anticancer chemotherapy (cisplatin)-induced vomiting has played a pivotal role in the identification and introduction of new classes of “designer” antiemetics such as 5-HT3- and NK1-receptor antagonists for use in clinical oncology. The importance of the use of cisplatin as an emetic in ferrets in the development of 5-HT3 receptor antiemetics cannot be overstated, since prior research often utilized apomorphine as the emetogen against which such antagonists are ineffective. On the other hand, based upon its well-accepted mechanism of action, it is also difficult to comprehend why peripherally administered serotonin is an effective emetogen in the shrew but not in the ferret. To further complicate the puzzle, it has been clearly demonstrated in this volume that the L-type calcium channel antagonist nidedipine is a new class of antiemetic which has potent and broad-spectrum antiemetic efficacy in the least shrew against selective/nonselective agonists of serotonin 5HT3-, dopamine D2/3-, tachykinin NK1- and muscarinic M1-receptors. However, it fails to suppress cisplatin-induced vomiting, unless nidedipine is combined with a 5-HT3-receptor antagonist. Subsequently, the emetic/antiemetic contributions of diverse serotonergic receptors are considered, followed by separate manuscripts discussing the interaction of serotonin 5-HT3- and tachykinin NK1-receptors at the calcium level, and the role of activation of such emetic receptors on vagal neurocircuits in the regulation of nausea and vomiting. The antiemetic actions of dexamethasone are discussed next, followed by detailing the neurochemical mechanisms of (i) post-operative nausea and vomiting; (ii) opioid-induced nausea and vomiting; (iii) cyclic vomiting; and (iv) bacterial- and viral-induced emesis. Human and animal models of
0014-2999/$ - see front matter & 2013 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.ejphar.2013.12.012
nausea are considered next, followed by manuscripts detailing regulation of nausea and vomiting by cannabinoids and endocannabinoids in different emesis models, and methods to manipulate activation of cannabinoid CB1 and vanilloid TRPV1 receptors to protect against highdose cisplatin-induced vomiting in a potent manner. Thereafter, the downstream receptor signaling of cyclophosphamide-induced vomiting is compared with those of cisplatin. The potential of development of new classes of antiemetics affecting post-receptor signal transduction mechanisms is also discussed. The relevance of basic science in both the study of emesis and development of antiemetics is bridged by our clinical colleagues in the applications of available antiemetics for the prevention of nausea and vomiting due to chemotherapy (CINV) or radiation, as well as anticipatory nausea and vomiting due to CINV. The clinical utilization of the nonselective antiemetic agent olanzapine is also described followed by discussions on nausea and vomiting in advanced cancer, as well as prognostic factors for CINV. Finally, the international antiemetic therapy guidelines for the prevention of CINV are presented. I am deeply saddened to inform our colleagues and readers of the European Journal of Pharmacology that our contributing colleague Dr. Howard S. Smith passed away on May 8, 2013. At the time of his passing, Dr. Smith was an anesthesiologist and pain management specialist at Albany Medical Center. Dr. Smith wrote 90% of his current article which was completed by his colleagues. Dr. Smith has made significant contributions in the area of emesis, particularly on opioidinduced nausea and vomiting. Perhaps we could console ourselves by the wise sayings of the great Eastern poet and Philosopher Saadi of Shiraz:
Men (mankind) with good deeds never die
Dead is someone of whom no one remembers
Although we all have research and discovery imprinted in our hearts, we also do enjoy seeing patients and/or teaching the new generation of allopathic and osteopathic medical students and medical graduates for continuing medical education. As such we impart significant knowledge to them. At the end of this volume we have contributed over 40 multiple choice questions to test the knowledge of our students and colleagues in the area of nausea and vomiting. Finally, I would like to take this opportunity to thank Dr. Nijkamp for inviting me to lead this project and my co-editors Drs. John Rudd, Karen Jordan and David Warr for their excellent contributions and review of the enclosed articles by leading researchers in the field.
Professor of Pharmacology, Associate Dean Nissar A. Darmani Basic Medical Sciences and Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA
