摘要:

&NA;Lubeluzole (R 87926, JK 8792, Prosynap®), a benzothiazole derivative, is a neuroprotectant under development with Janssen (Johnson and Johnson) for the treatment of acute ischaemic stroke. Its neuroprotective effects are favoured to be mediated via the prevention of nitric oxide-induced neuronal cell death. Janssen has initiated the regulatory approval process for lubeluzole in the USA and Europe. However, the case made for approval hinges on a meta-analysis of functional outcome in 2 independent phase III trials, whereby, to resolve a significant level of efficacy, it was necessary to exclude patients over 75 years of age with severe stroke.Phase III trials are also being conducted in Europe, Canada and Australia. Janssen-Kyowa (a joint venture between Janssen and Kyowa Hakko) is also developing lubeluzole in Japan, where it is currently undergoing phase I clinical trials.Lubeluzole is a novel benzothiazole compound that may exert its neuroprotective effects by inhibition of the glutamate-activated nitric oxide synthase pathway. High doses of lubeluzole have been associated with adverse cardiovascular events and safety concerns. However, lower doses of lubeluzole have been associated with modest clinical improvement and no major toxicity issues. Lubeluzole has had a favourable effect on mortality in patients with mild to moderate ischaemic stroke, but does not appear to be beneficial in severe stroke. Large studies to further define the role of lubeluzole in acute ischaemic stroke are underway.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Nalmefene (JF 1, nalmetrene, NIH 10365, ORF 11676, Incystene®, Arthrene®, Cervene®, Revex®) is an opioid receptor antagonist with a potency approximately twice that of naloxone as well as a longer duration of action. It was originally synthesised by Rockefeller University and licensed to Key Pharmaceuticals (Schering-Plough). IVX BioSciences (formerly IVAX Corporation) has exclusive worldwide patent rights to nalmefene (obtained from Key Pharmaceuticals). An exclusive licensing agreement exists between Ohmeda (the BOC Group) and IVX BioSciences for marketing rights to the parenteral form in the US, Canada and Western Europe. Ohmeda's Pharmaceutical Products Division has since been acquired by, and integrated into, Baxter International. The oral form of nalmefene is also licensed to SS Pharmaceutical for Japan. Nalmefene is also licensed to Nycomed Amersham.Nalmefene was launched in the US and preregistration in Canada and the UK for the reversal of the effects of opioids and the management of opioid overdose. The compound is also in preregistration in the US and in phase II trials in Japan and South Korea for the treatment of interstitial cystitis. In the US, nalmefene is in clinical trials for the treatment of recalcitrant pruritis of cholestasis, and stroke (the injectible form, Cervene®); and phase II trials for CNS trauma, rheumatoid arthritis and shock. Phase II trials for rheumatoid arthritis are also underway in Japan and South Korea. In addition, the oral formulation of nalmefene is in phase II trials in the US for the treatment of alcoholism. Nalmefene also appears to have potential for the treatment of antipsychotic-induced tardive dyskinesia, and may have potential for allergic rhinitis and for improving transplant donor organ function.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;OPC 14117 is a novel cerebroprotective agent with CNS-stimulating activity. It is thought to act by inhibiting lipid peroxidation and has displayed neuroprotective effects against cerebral ischaemia in mice and rats. OPC 14117 is undergoing phase II clinical trials in the USA with Otsuka as a potential treatment for CNS trauma and cerebral ischaemia. In addition, a phase I/II trial in patients with HIV dementia has been conducted in the USA in collaboration with the Dana Consortium on Therapy for HIV Dementia and Related Cognitive Disorders. Otsuka also appears to be investigating the drug in phase II clinical trials in the USA and Japan for the treatment of Parkinson's disease and Huntington's disease.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Gangliosides are naturally-occurring complex glycosphingolipids that are important components of mammalian cell membranes, particularly nerve cell, plasma and intracellular membranes.In vitroandin vivoexperimental animal studies have demonstrated that gangliosides such as Fidia Pharmaceutical's siagoside (GM1; Sygen®) may stimulate or accelerate the repair of neurons after nervous system damage. Phase II clinical trials of siagoside in patients with Parkinson's disease are underway in the USA. A clinical trial conducted in Italy in patients with stroke indicates that early intervention with siagoside may improve neurological outcome. US clinical trial results suggest that siagoside may enhance neurological recovery after spinal cord injury. Clinical trials investigating the efficacy of siagoside in the treatment of Alzheimer's disease have reported no improvements in cognition.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;TAK 218 is a 5-aminocoumaran that is under development with Takeda in Japan. It is undergoing phase II clinical trials in Japan and phase I trials in the USA for the treatment of stroke. TAK 218 produces neuroprotection by 3 different ways: modulation of sodium channels, lipid peroxidation inhibition and suppression of aberrant dopamine release. It may have potential for treatment during the acute phase of cerebrovascular disease and after traumatic central nervous system injury.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Trafermin (KCB 1, CAB 2001, Fiblast®), a recombinant form of basic fibroblast growth factor known as 2-155-basic fibroblast growth factor (human clone &lgr;KB7/&lgr;HFL1 precursor reduced), is a potent angiogenic, heparin-binding peptide with a molecular weight of 17 124D. It has potential in the treatment of conditions requiring the stimulation of blood vessels and tissue repair. Scios was the first company to clone and produce recombinant human basic fibroblast growth factor and holds patents in the US and Europe covering its manufacture, use and sale.Scios has an agreement with Wyeth-Ayerst (American Home Products) for the development and commercialisation of trafermin in the US in the treatment of neurological and cardiovascular disorders. Under the agreement, the 2 companies will share development costs and profits. Wyeth-Ayerst also receives exclusive marketing rights outside of North America and certain Pacific Rim countries. Scios is leading development of trafermin in vascular indications, whereas, Wyeth-Ayerst is leading its development in the treatment of stroke. In 1988 Kaken (Japan) licensed trafermin from Scios for development and marketing rights in China, Hong Kong, Japan, Korea and Taiwan for all indications. Trafermin is also licensed to Merck KGaA who is conducting preclinical studies for treatment of soft tissue ulcers.A phase III trial in the US for the treatment of stroke was terminated because of an unfavourable risk:benefit ratio in trafermin-treated patientsvsthose receiving placebo. Interim results from an ongoing trial in Europe, which has a different dosing regimen (24hvs8h infusion), have raised no such concerns. Trafermin is also in phase II trials in the US for peripheral vascular disease and coronary artery disease. Kaken has submitted an NDA in Japan for the treatment of intractable skin ulcers. Kaken is investigating trafermin in preclinical trials for the treatment of bone fractures, periodontosis and osteoporosis in Japan.Clinical investigation into the use of locally administered pellets containing trafermin, in patients undergoing coronary artery bypass surgery, is continuing at the Montefiore Medical Center in the US.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;YM 900 (YM 90K) is a selective and potent AMPA-type glutamate receptor antagonist. YM 900 is currently undergoing phase II studies for the treatment of stroke with Yamanouchi in Japan. YM 900 also has potential for the treatment of Alzheimer's disease, as shown in preclinical testing, and appears to be undergoing phase I trials for the treatment of seizures. YM 900 is in preclinical development with Zeneca in the USA as a potential antiparkinsonian agent.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;ZD 9379 is an orally active glycine antagonist that is entering phase II clinical investigation with Zeneca in the UK for the treatment of acute stroke and pain.ZD 9379 is a potent full antagonist at the glycine site of the NMDA receptor. It resulted in a substantial decrease in infarct size and in the number of spreading cortical depressions in a rat model of permanent cerebral ischaemia, without causing any observable adverse effects. This drug is the first glycine site antagonist to exhibit simultaneous inhibition of spreading depressions and infarct volume. It remains to be determined whether the correlation between the number of spreading depressions and infarct volume may reflect a causal relationship.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Ziconotide (CI 1009, SNX 111), the synthetic form of the cone snail peptide &ohgr;-cenotoxin M-VII-A, is a neurone-specific calcium channel blocker that is being developed as an analgesic agent by Neurex Corporation (a subsidiary of Elan Corporation). There are positive first phase III trial results regarding the selectivity and effectiveness of ziconotide in the treatment of severe neurogenic pain including post-herpetic neuralgia (shingles), phantom limb syndrome and reflex sympathetic dystrophy. Ziconotide has shown to be effective in alleviating severe neurogenic pain in patients with HIV who had failed opiate treatment. Ziconotide has completed a second phase III clinical trial for the treatment of intractable, noncancer pain as well as cancer pain in patients who demonstrated a nonresponse or intolerance to opiate therapy. Ziconotide has entered phase II clinical trials with Neurex for the management of severe postoperative pain after major thoracic, orthopaedic and abdominal surgery. Both the epidural and intrathecal routes of administration will be investigated.Ziconotide for the treatment of chronic pain is being developed in cooperation with Medtronic using their SynchroMed® implantable pump for direct administration into the spine. Under a cost-sharing agreement, Medtronic has worldwide rights to ziconotide for spinal administration, while Neurex retains manufacturing rights and rights for further development of ziconotide as an acute analgesic agent. Warner-Lambert has licensed rights worldwide except for Japan and East Asia for use in neurological indications. Ono had rights to Neurex-discovered neurone-specific calcium channel blockers for Japan and East Asia, however this agreement was terminated.Ziconotide is undergoing phase III clinical trials with Neurex (in collaboration with Warner-Lambert) in the US and Europe for the prevention of ischaemic brain damage following stroke and severe head trauma. Phase III trials are also underway in Japan. The US FDA had put a clinical hold on ziconotide because of recumbent hypotension in a trial for the prevention of brain damage after closed head trauma and coronary artery bypass grafting, but this hold has since been lifted.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Promising immunosuppressive drugs designed to prevent rejection have been developed recently. Two monoclonal antibodies directed against the interleukin-2 (IL-2) receptor, daclizumab and basiliximab, have been shown to significantly reduce the incidence of acute rejection without increasing adverse events. Sirolimus (rapamycin), an agent that inhibits T- and B-response at a later stage than cyclosporin, has been shown to be synergistic with cyclosporin in experimental and clinical studies. Ongoing clinical trials have reported that in renal transplantation high doses of sirolimus are as effective as cyclosporin. SDZ-RAD, a derivative of sirolimus, is also under investigation. FTY-720 another promising drug, prolonged the survival of allografts and synergised with cyclosporin and sirolimus in experimental models. Gusperimus (deoxyspergualin), which inhibits IL-1 synthesis, was useful in reversing early and late acute rejection in clinical trials. Antisense oligonucleotides which interfere with intercellular adhesion molecules which are important in rejection, gave encouraging results in primate renal allografts.The availability of these new drugs will be able to further abate the risk of rejection in organ transplantation. However, caution is warranted with their use in order to avoid the risks of over immunosuppression. Today excellent results can be obtained with the available drugs. Newer immunosuppressive schedules should be designed, not only to reduce the risk of rejection, but also to obtain a better therapeutic index that allows a further improvement of the graft survival while minimising the comorbidity and drug-related toxicity.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS