摘要:

Significant progress has been made in recent years in developing more effective means of preventing nausea and vomiting induced by cancer chemotherapy. With appropriate application of currently available antiemetic regimens, the majority of patients with cancer who are receiving chemotherapy can anticipate experiencing no emesis during their treatment. Nevertheless, incompletely controlled emesis remains a problem for a significant percentage of patients. Persistent challenges include delayed emesis and emesis following high-dose chemotherapy regimens. The goal of complete prevention of emesis in all patients remains elusive. Therefore, there is a strong rationale for investigating new antiemetic approaches.New antiemetic agents currently under development target the neurotransmitters serotonin (5-hydroxytryptamine; 5-HT) and substance P. A number of new selective antagonists of serotonin 5-HT3 receptors are in clinical trials. Given the lack of clinically significant differences between the available 5-HT3 receptor antagonists, it appears unlikely that any of these new agents will have substantial advantages over currently approved agents. Several other serotonin receptors have been targeted including the 5-HT4, 5-HT1A and 5-HT2A receptors. Of these approaches, only agonism of the 5-HT1A receptor has produced an agent that has proceeded into clinical testing.The most exciting new class of antiemetics currently under development focuses on antagonism of the effects of the neurotransmitter substance P. Results of early clinical trials with tachykinin neurokinin NK1 receptor antagonists demonstrate enhanced control of acute emesis with their addition to currently available agents and promising activity in controlling delayed emesis. Available evidence would strongly suggest that this class of agents will represent the next important advance in efforts to control nausea and vomiting induced by chemotherapy.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

All drugs appearing in the Adis Profile Summary table have been selected based on information contained inR&D InsightTM, a proprietary product of Adis International. As the emphasis ofDrugs in R&Dis on the clinical potential of new drugs, selection of agents for full profile is based on the extensiveness of available data. Information on all drugs in clinical development, as identified fromR&D InsightTM, is included in the summary table. Information and/or profiles of agents in preclinical development may be included as appropriate.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;CJ 11974, an azabicyclooctane, is a novel nonpeptidic, neurokinin NK1substance P receptor antagonist under development with Pfizer in the US. It is in phase III trials for the treatment of chemotherapy-induced emesis and is also undergoing preclinical investigation as a potential analgesic agent.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Itasetron (DAU 6215, U 98079) is a potent and selective serotonin 5-HT3receptor antagonist currently in phase II/III clinical trials in Germany, the US and Japan with Boehringer Ingelheim as a potential oral antiemetic agent for use in cancer patients. Itasetron is also in early phase II clinical trials as an anxiolytic agent in Germany and is undergoing preclinical investigation in Italy for anxiety and as a potential cognition enhancing agent. It may also have potential as an antipsychotic agent. Pharmacia & Upjohn has licensed itasetron for joint development and marketing worldwide.Itasetron has a favourable pharmacokinetic profile compared with other currently available 5-HT3antagonist antiemetic agents.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Lerisetron (F 0930RS, F 0930) is a serotonin 5-HT3receptor antagonist with potential as an antiemetic agent. Lerisetron is currently undergoing phase II trials with FAES in Spain. With the exception of Spain and Portugal, lerisetron is available for licensing worldwide.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Levosulpiride (RV 12309, Levopraid®) is a potent dopamine D2receptor blocker originated by Ravizza and licensed to Alter. It appears to have antiemetic activity as well as therapeutic potential in patients with depression and psychosis. Levosulpiride appears to be more effective and better tolerated than the racemic compound, sulpiride. Levosulpiride has been approved in Italy, and is undergoing preclinical trials in France and the UK, as an antidepressant, antiemetic and antipsychotic. It has also been approved as an antidepressant in Spain. Levosulpiride also appears to have completed clinical trials in the treatment of dyspepsia and reflux oesophagitis in Italy and Korea.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;MK 869 (L 754030, MK 0869) is a substance P antagonist selective for neurokinin NK1receptors that is undergoing phase II clinical trials with Merck & Co. in the US as a potential treatment for acute and delayed chemotherapy-induced emesis. Phase II trials for anxiety and schizophrenia are also in progress. The drug was in development as an antidepressant but studies in this indication were suspended in early 1999 as a result of an inconclusive phase II dose-finding study.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Palonosetron (RS 25259, RS 25259 197) is a novel high affinity serotonin 5-HT3receptor antagonist. There is some evidence to suggest that this compound interacts with the receptor in a different manner to granisetron. Roche Bioscience is conducting phase III clinical trials in the US with palonosetron for the treatment of postoperative- and chemotherapy-induced emesis.Palonosetron was more effective than ondansetron in preventing chemotherapy-induced emesis in preclinical studies. Preliminary clinical studies indicate that palonosetron reduces postoperative vomiting, but like other 5-HT3antagonists, seems to increase postoperative headaches. Palonosetron has had questionable efficacy in high risk patients undergoing major procedures. However, these results are but preliminary and the future of palonosetron as an antiemetic agent will be determined by the results of large, comparative clinical trials.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Zatosetron (LY 277359, LY 19167) is a serotonin 5-HT3receptor antagonist undergoing phase III clinical trials with Eli Lilly in the US for treatment of chronic anxiety. Phase II trials in Japan have been discontinued. Zatosetron has also shown promise as an antiemetic agent and is undergoing phase II trials in the US for this indication. AUS phase II clinical trial of zatosetron failed to demonstrate significant improvement in patients with migraine when the drug was administered as a single IV infusion.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

All drugs appearing in the Adis Profile Summary table have been selected based on information contained inR&D InsightTM, a proprietary product of Adis International. As the emphasis ofDrugs in R&Dis on the clinical potential of new drugs, selection of agents for full profile is based on the extensiveness of available data. Information on all drugs in clinical development, as identified fromR&D InsightTM, is included in the summary table. Information and/or profiles of agents in preclinical development may be included as appropriate.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS