摘要:

Acute ischaemic strokes can potentially be treated by 2 different mechanisms: lysing the thrombus to enhance brain perfusion or salvaging brain tissue directly. Neuroprotective agents are designed to try to salvage brain tissue. They work either during acute ischaemia or during reperfusion, when additional brain injury may occur.Despite the completion of a number of clinical trials investigating neuroprotective agents that have various mechanisms of action, as yet no effective agent has been identified. Some drugs, such asN-methyl-D-aspartate (NMDA) receptor antagonists and anti-leucocyte adhesion agents, have been limited by adverse effects and drug reactions. However, the development of other agents in these classes that have better risk to benefit ratios may lead to an effective neuroprotective drug. Other drugs, including citicoline, clomethiazole and nalmefene, have more efficacy in certain patient subgroups than in the stroke population as a whole. Therefore, targeting these agents toward the groups in which they are most likely to work, such as patients with a certain size of stroke, may uncover efficacy. Encouragingly, a number of drugs that are in the early stages of development, such as YM 872, Bay X 3702 and BMS 204352, appear to offer new hope for neuroprotection.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

All the 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 a 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;ARR 15896AR (ARR 15896, ARL 15896, ARL 15896AR, FPL 15896AR, FPL 15896) is a noncompetitive NMDA antagonist which is in development with Astra for intravenous administration in acute stroke. The compound is similar to remacemide, and appears to have completed phase I trials in Europe, and phase II trials are underway in the USA. ARR 15896AR may also have potential for the treatment of epilepsy. The drug was originally in development with Fisons, who sold their R&D activities to Astra.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;BAY X 3702 is the first selective and high-affinity serotonin1A receptor agonist to have potent neuroprotective activity in rodent models of permanent focal cerebral ischaemia and acute subdural haematoma with an extended therapeutic time window and a good toxicological profile. Consequently, BAY X 3702 may represent a new pharmacological approach for the the treatment of acute ischaemic stroke.BAY X 3702 is a novel aminomethylchroman derivative with high affinity for serotonin1A receptors. It is in phase II of development with Bayer in Germany for acute ischaemic stroke and traumatic brain injury.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;BIII 277CL (BIII 277), a benzomorphan derivative, is a selective, noncompetitive NMDA antagonist under development as a neuroprotective. BIII 281CL is the enantiomer of BIII 277CL which exhibits less potent inhibition of NMDA.Boehringer Ingelheim is currently conducting preclinical trials with BIII 277CL in Germany for the potential treatment of stroke. Phase II clinical trials appear to be underway in Japan.BIII 277CL a stereoisomeric 6,7-benzomorphan derivative with high affinity and specificity for the NMDA receptor, has been chosen as an optimised candidate for pharmacological investigation of neuroprotective properties. The use-dependence of BIII 277CL-induced blockade of NMDA receptors should contribute to a favourable pharmacokinetic profile for this compound.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Clomethiazole (chlormethiazole, Zendra®) is undergoing phase III clinical investigation with Astra in Europe, the USA and Canada for the treatment of acute stroke. It is currently being used clinically to treat seizures, alcohol withdrawal and as a sedative. Although the mechanism of action of clomethiazole is not fully understood, studies suggest that it may act by stimulating the GABA receptor.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

CPC 211 (Ceresine®) is a neuroprotective agent currently undergoing phase II clinical trials with Cypros Pharmaceutical in the USA for intravenous use in patients with closed head injuries and stroke patients. It is also in clinical trials for patients with spinal cord injury. The US FDA has granted the drug expedited development status for the treatment of acute head injury. Trials are also being conducted with an oral form of CPC 211.CPC 211 was originated at the Michigan State University and is available for licensing outside of North America.CPC 211 normalises elevated lactic acid levels by stimulating a specific enzyme responsible for transporting lactic acid into mitochondria. CPC 211 is reported to reduce serum lactic acid levels in patients with lactic acidosis.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Gavestinel (GV 150526A, GV 150526), an indole derivative, is a glycine-site NMDA receptor antagonist that is in worldwide phase III trials with Glaxo Wellcome for the treatment of ischaemic and haemorrhagic stroke. The target number of patients for these trials is 3000.Gavestinel is a potent and selective antagonist at the glycine site of the NMDA receptor. It has an excellent neuroprotective profile in animal models of stroke, with a wide therapeutic window. As such, gavestinel has the potential to be an important compound in the treatment of stroke.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Hu23F2G (23F2G, LeukArrestTM) is a humanised leukointegrin monoclonal antibody that is in phase II trials with ICOS Corporation and Abbott in the US for the treatment of trauma-induced haemorrhagic shock. ICOS has initiated a phase II study of Hu23F2G in patients with multiple sclerosis undergoing acute exacerbations. No significant clinical benefit was seen in this trial, however an additional phase II trial has been initiated using a multiple dosing regimen. Phase II trials in patients with myocardial infarction (MI) and in patients with ischaemic stroke have been completed. The study in patients with MI was being conducted by the Mayo Physician Alliance for Cardiovascular Trials, an affiliate of the Mayo Clinic in Rochester, USA. ICOS Corporation humanised the monoclonal antibody to the CD18 receptor on leukocytes and has exclusive rights to Hu23F2G in the USA. Abbott has exclusive rights to Hu23F2G outside the USA.ICOS is also investigating the potential of Hu23F2G in the treatment of cerebral vasospasm, head trauma and restenosis in preclinical studies. Hu23F2G may also have potential in the treatment of acute peripheral arterial occlusion and in the preservation of solid transplant organs; these indications are at the research stage of development.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Licostinel (ACEA 1021), a member of a series of compounds called kappagems, is a potent, selective and competitive antagonist at the glycine site on the N-methyl-D-aspartate (NMDA) receptor. Licostinel has demonstrated neuroprotective and anticonvulsant activity. The compound, originated by Acea, was being developed by CoCensys and Novartis in the USA as a neuroprotective agent for the treatment of stroke and head trauma. However, Novartis decided not to continue development when crystals of licostinel were found in the urine of some participants in a phase I study. CoCensys retains all rights to the drug, which it is continuing to evaluate in phase II clinical trials. It is also undergoing preclinical assessment for anticonvulsant activity and for use in cognition disorders.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS