A Randomized, Double-Blind, Placebo-Controlled Four Week Study of the Efficacy and Safety of Four Doses (0.05 mg, 0.1 mg, 0.25 mg, 0.5 mg) of Aplindore MR Tablets vs. Placebo in Idiopathic Restless Legs Syndrome.

This is a clinical trial to be conducted at multiple sites in the USA. Patients diagnosed with moderate to severe Restless Legs Syndrome will be randomly allocated to one of 5 treatment arms in the study. The 5 arms include 4 arms with different doses of aplindore MR tablets and 1 placebo arm. The treatment will be taken once a day. The study is blinded and neither patients, nor the investigators, will know what treatment the patient is receiving. Patients will be assigned a dose and will be maintained at that dose for several weeks (2 treatment arms include a short titration period). The entire study will take about 6 weeks. The study will measure how effective aplindore is in decreasing symptoms of Restless Legs Syndrome, and will also assess the safety and tolerability of aplindore.

开始日期2009-02-01

申办/合作机构

Neurogen Corp.

NCT00809302 / Terminated临床2期

A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Three Doses of Aplindore MR (1, 3, and 6 mg Twice Daily) in Patients With Early Parkinson Disease (APLIED)

This is a clinical trial to be conducted at multiple Parkinson Study Group (PSG) sites in the USA. Patients with early Parkinson disease will be randomly allocated to one of 4 arms in the study. The 4 arms include 3 arms with different doses of aplindore MR tablets and 1 placebo arm. The study drug will be taken twice a day (BID). The study is blinded and neither subjects, nor the investigators, will know what treatment the subject is receiving. Investigational study drug will be adjusted to the assigned dosage and then maintained at that dosage for the balance of the 12 week follow-up period. The entire study will take about 13 weeks. The study will assess the safety and tolerability of aplindore and measure how effective aplindore is in improving movement and other effects of Parkinson disease.

开始日期2008-12-01

申办/合作机构

Neurogen Corp.

NCT00626418 / Completed临床2期

A Single-blind, Placebo Controlled Sleep Laboratory Study of the Acute Effects of Aplindore in Restless Legs Syndrome

The purpose of this study is to assess the efficacy and tolerability of single doses of aplindore compared to placebo in RLS. Patients will be required to spend 5-8 nights in a sleep laboratory. This includes 1 adaptation night, 1 placebo night, and 3-6 drug treatment nights. Ascending doses of active drug will be administered on study nights 3 through 5 to determine the maximum well tolerated efficacious dose (defined as a decrease in Periodic Limb Movement Index (PLMI) of at least 50% from placebo baseline). If an efficacious dose cannot be identified the Investigator in consultation with the sponsor may decide to examine higher doses in up to 3 additional PSG nights in an attempt to identify a tolerable efficacious dose. This study will utilize up to 24 evaluable patients, each meeting International Classification of Sleep Disorders (ICSD-2) diagnostic criteria for primary RLS who are not currently taking any RLS medication including DAs ( and L-dopa) or who are able to discontinue their RLS medication at least 5 half-lives prior to the adaptation night.

开始日期2008-02-01

申办/合作机构

Ligand Pharmaceuticals, Inc.

100 项与 Aplindore Fumarate 相关的临床结果

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100 项与 Aplindore Fumarate 相关的转化医学

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100 项与 Aplindore Fumarate 相关的专利（医药）

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项与 Aplindore Fumarate 相关的文献（医药）

2010-01-01·Journal of Neural Transmission4区 · 医学

The dopamine D2 receptor partial agonist aplindore improves motor deficits in MPTP-treated common marmosets alone and combined with l-dopa

4区 · 医学

Article

作者: Andree, Terrance H. ; Hurtt, Mark R. ; Stack, Gary ; Hoffman, Diane C. ; Hansard, Matthew ; Pitler, Thomas A. ; Jenner, Peter ; Jackson, Michael John ; Smith, Lance A. ; Kehne, John H.

Dopamine replacement therapy in Parkinson's disease (PD) using L-dopa is invariably associated with a loss of drug efficacy ("wearing off") and the onset of dyskinesia. The use of dopamine receptor partial agonists might improve therapeutic benefit without increased dyskinesia expression but may antagonise the effects of L-dopa. We now examine the effects of the novel high affinity, dopamine D(2) receptor partial agonist, aplindore alone and in combination with L-dopa in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmoset. In non-dyskinetic MPTP treated animals, aplindore (0.05-1.0 mg/kg p.o.) produced a dose-dependent reversal of motor disability and an increase in locomotor activity that was maximal at doses of 0.2 mg/kg and above. In animals previously exposed to L: -dopa to induce dyskinesia, escalating and repeated dosing of aplindore (0.05-0.5 mg/kg p.o.) produced a sustained, dose-related improvement in motor disability and an increase in locomotor activity. The effects were maximal at a dose of 0.1 mg/kg and above and not different from those produced by L-dopa (12.5 mg/kg plus carbidopa 12.5 mg/kg p.o.). Aplindore administration also led to dose-dependent expression of dyskinesia but at 0.1 mg/kg, this was significantly less intense than that produced by L-dopa. Administration of aplindore (1.0 mg/kg p.o.) in combination with L-dopa (2.5 mg/kg plus carbidopa 12.5 mg/kg p.o.) did not inhibit the reversal of motor deficits but improved motor disability and increased both locomotor activity and dyskinesia expression equivalent to that produced by L-dopa (12.5 mg/kg plus carbidopa 12.5 mg/kg p.o.). These data suggest that dopamine receptor partial agonists would be effective in the treatment of Parkinson's disease and would not inhibit the beneficial actions of L-dopa.

2006-12-01·European Journal of Pharmacology3区 · 医学

Aplindore (DAB-452), a high affinity selective dopamine D2 receptor partial agonist

3区 · 医学

Article

作者: Pausch, Mark H. ; Hornby, Geoff ; Stack, Gary ; Popiolek, Mike ; Sullivan, Kelly ; Jiang, Li-Xin ; Brennan, Julie ; Marquis, Karen L. ; Heinrich, Julia N. ; Andree, Terrance H. ; Lai, Margaret H.

The pharmacology of aplindore (DAB-452) was characterized in CHO-K1 cells stably transfected with the human dopamine D(2) receptor short isoform (CHO-D(2s)) and in a behavioral model for post-synaptic agonism in rats. In [(3)H]-spiperone competition binding studies, aplindore showed high affinity for dopamine D(2) and D(3) receptors and low affinity for the dopamine D(4), serotonin (5-HT)(1A), 5-HT(2) receptors and the alpha1-adrenoceptor. The high potency partial agonist activity of aplindore was demonstrated in [(35)S]guanosine 5'-O-(3-thiotriphosphate) ([(35)S]GTPgammaS) binding, extracellular signal-regulated kinase (ERK)-phosphorylation and intracellular calcium flux assay using fluorometric plate reader ([Ca(2+)](i)-FLIPR) format. The [Ca(2+)](i)-FLIPR assay was conducted with CHO-D(2S) receptor cells also stably expressing chimeric G(alphaq/o)-proteins. In all assay modalities, the potencies and intrinsic activities of aplindore were lower than dopamine and higher than aripiprazole. In contrast to the [(35)S]GTPgammaS binding and ERK-phosphorylation assays, the [Ca(2+)](i)-FLIPR assay was able to detect the low partial agonist activity of SDZ 208-912. In unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats, aplindore induced contralateral turning, which was blocked by the dopamine D(2) receptor antagonist raclopride. The dopamine D(2) receptor selective partial agonist profile of aplindore suggests that it should be effective for the treatment of dopaminergic-based disorders, such as schizophrenia and Parkinson's disease.

2006-10-01·British Journal of Pharmacology2区 · 医学

Assays for enhanced activity of low efficacy partial agonists at the D₂ dopamine receptor

2区 · 医学

Article

作者: Saisch, S. G. N. ; Lin, H. ; Strange, P. G.

Background and purpose:Low efficacy partial agonists at the D2 dopamine receptor may be useful for treating schizophrenia. In this report we describe a method for assessing the efficacy of these compounds based on stimulation of [35S]GTPγS binding.Experimental approach:Agonist efficacy was assessed from [35S]GTPγS binding to membranes of CHO cells expressing D2 dopamine receptors in buffers with and without Na+. Effects of Na+ on receptor/G protein coupling were assessed using agonist/[3H]spiperone competition binding assays.Key results:When [35S]GTPγS binding assays were performed in buffers containing Na+, some agonists (aripiprazole, AJ‐76, UH‐232) exhibited very low efficacy whereas other agonists exhibited measurable efficacy. When Na+ was substituted by N‐methyl D‐glucamine, the efficacy of all agonists increased (relative to that of dopamine) but particularly for aripiprazole, aplindore, AJ‐76, (−)‐3‐PPP and UH‐232. In ligand binding assays, substitution of Na+ by N‐methyl D‐glucamine increased receptor/G protein coupling for some agonists ‐. aplindore, dopamine and (−)‐3‐PPP – but for aripiprazole, AJ‐76 and UH‐232 there was little effect on receptor/G protein coupling.Conclusions and implications:Substitution of Na+ by NMDG increases sensitivity in [35S]GTPγS binding assays so that very low efficacy agonists were detected clearly. For some agonists the effect seems to be mediated via enhanced receptor/G protein coupling whereas for others the effect is mediated at another point in the G protein activation cycle. AJ‐76, aripiprazole and UH‐232 seem particularly sensitive to this change in assay conditions. This work provides a new method to discover these very low efficacy agonists.British Journal of Pharmacology (2006) 149, 291–299. doi:10.1038/sj.bjp.0706866

100 项与 Aplindore Fumarate 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03214	-	-	DB06620

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
帕金森病	临床3期	-	Pfizer Inc.	-
帕金森病	临床3期	-	Ligand Pharmaceuticals, Inc.	-
不宁腿综合征	临床2期	美国	Ligand Pharmaceuticals, Inc.	2008-02-01
不宁腿综合征1型	临床1期	美国	Neurogen Corp.	2009-02-01
帕金森病（青年型、早发型）	临床1期	美国	Neurogen Corp.	2008-12-01
精神分裂症	临床1期	美国	Wyeth Ltd. (India)	-