摘要:

&NA;TBC 11251 (IPI 1040), a selective endothelin-A (ET-A) receptor antagonist, has potential for use in the treatment of congestive heart failure. It is undergoing phase I development in the UK. In the US it is undergoing phase IIa development in the IV form and phase I in the oral form with Texas Biotechnology. The phase IIa study was prematurely terminated as statistically significant results were achieved in fewer patients than expected. Asecond phase IIa study in 24 patients, using a higher dose, has been completed and also demonstrated a statistically significant improvement versus placebo.These studies used an IV formulation, but Texas Biotechnology plans to initiate phase II trials using an oral form. TBC 11251 is also at the preclinical stage of development for the treatment of pulmonary hypertension and is expected to be useful in treating diseases such as hypertension, stroke,myocardial infarction, chronic obstructive pulmonary disease and acute renal failure.Texas Biotechnology has entered into an agreement with LG Chem for the development of TBC 11251. LG Chem will market the drug in Asia, excluding Japan.

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;Aripiprazole (OPC 14597) is a quinolinone derivative under development as a potential antipsychotic agent. It is currently undergoing phase III clinical trials with Otsuka in Japan and the US.Aripiprazole is thought to act as a presynaptic dopamine D2 autoreceptor agonist and as a postsynaptic dopamine D2 receptor antagonist. The pharmacological profile of aripiprazole suggests that it may be effective against both the positive and negative symptoms of schizophrenia.Aripiprazole is a quinolinone derivative of OPC 4392. Both of these compounds exhibit unusual functional profiles, with dual agonist/antagonist activity at dopamine D2receptors. Whereas the postsynaptic antagonist actions of OPC 4392 are observed at much higher doses than those that elicit presynaptic agonism, these opposing effects occur at equivalent doses of aripiprazole. Clinical testing of OPC 4392 was terminated because of some exacerbation of positive symptoms. Early clinical testing of aripiprazole, however, suggest efficacy against positive and negative symptoms of schizophrenia, with little induction of extrapyramidal symptoms.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Blonanserin (AD 5423) is a combined dopamine D2and serotonin 5-HT2receptor antagonist, currently undergoing phase III clinical trials in Japan with Dainippon Pharmaceutical as a potential antipsychotic agent. Blonanserin is unrelated structurally to typical antipsychotics or to newer agents such as risperidone. It is hoped that the combination of receptor blockade possessed by blonanserin will be effective against both the positive and negative symptoms of schizophrenia, with a low tendency to cause extrapyramidal symptoms.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;MCI 225 is a thienopyrimidine analogue currently undergoing phase II clinical trials with Mitsubishi Chemical in Japan as an antidepressant. The mechanism of action of MCI 225 appears to involve inhibition of noradrenaline (norepinephrine) reuptake and turnover combined with antagonism at serotonin 5-HT3 receptors, which may contribute to its antidepressant effect and reduce its anticholinergic action. The compound has exhibited antidepressant activity at least as potent as tricyclic antidepressants in animal models. Mitsubishi Chemical has announced that itwill collaboratewith Taisho Pharmaceutical on phase III clinical testing of this compound in early 2000. In doing so, Mitsubishi Chemical hopes to accelerate development of MCI 225, and Taisho is looking to fortify its CNS drug operations.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;MKC 242 is a serotonin 5-HT1Aagonist undergoing phase II trials with Mitsubishi Chemical in Japan as a treatment for anxiety and depression. It is also being investigated in phase II trials in France as a therapy for depression. MKC 242 has potential in the treatment of irritable bowel syndrome, and is currently being investigated preclinically for this indication in Japan.MKC 242 is a potent and selective 5-HT1Areceptor agonist with anxiolytic and antidepressant-like effects in rats. The compound also appears to have an antiobsessional effect. Preclinical results suggest thatMKC 242 has similar pharmacological properties to the azapirones, but may possess a longer-lasting effect.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;NE 100 is a potent and selective &sgr;1-receptor antagonist with potential as an antipsychotic agent. NE 100 is currently undergoing phase II trials in Japan with Taisho. The compound may also be useful in the treatment of abnormal behaviour associated with cerebrovascular disorders (e.g. stroke) and senile dementia.NE 100 has no effect on dopamine or serotonin-related behaviour. NE 100 does, however, potently antagonise phencyclidine-induced behaviour in animal models. Selective and potent antagonism of central &sgr;-receptors may provide an alternative strategy for the treatment of schizophrenia.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Pazinaclone (A 77000, DN 2327) is a novel isoindoline derivative with a selective anxiolytic action. Although pazinaclone has a different chemical structure to the benzodiazepines, it has been found to bind to benzodiazepine receptors. The compound is currently being developed as an anxiolytic agent by Takeda. Pazinaclone is in phase III clinical trials in Europe, and phase II trials in Japan and the US.Pazinaclone is a relatively specific benzodiazepine BZ1receptor agonist in contrast to classical benzodiazepines. Pazinaclone has demonstrated anxiolytic activity in patients with generalised anxiety disorder. Pazinaclone may have a similar profile of adverse events to the classical benzodiazepines. However, pazinaclone is an interesting new compound and further clinical studies are warranted.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Perospirone (SM 9018), a novel serotonin 5-HT2and dopamine D2receptor antagonist, is currently undergoing phase III clinical trials with Sumitomo in Japan as a potential antipsychotic agent. Perospirone has only weak cataleptogenic and central depressant effects in animals. Perospirone has a profile of activity suggesting beneficial effects on both the positive and negative symptoms of schizophrenia. Perospirone is also undergoing phase II trials for cerebrovascular dementia in Japan.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;RS 8359 is a highly selective and reversible monoamine oxidase type A (MAO-A) inhibitor. RS 8359 is currently undergoing phase II clinical trials in Germany and phase I clinical trials in Japan with Sankyo as a potential antidepressant agent.The selectivity of RS 8359 for MOA-A is markedly greater than that of moclobemide. Early small-scale clinical studies, however, have not yet demonstrated any obvious efficacy or tolerability advantages with RS 8359 compared with moclobemide in the clinical setting.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS