A Double Blind, Randomized, Placebo Controlled, Crossover Study to Investigate the Anti-hyperalgesic Efficacy of a Single Dose of Fenobam on Heat/Capsaicin Induced Cutaneous Hyperalgesia in Adult Healthy Volunteers.

Our goal is to demonstrate that healthy volunteers treated with fenobam will develop a significantly reduced area of cutaneous hyperalgesia compared to volunteers treated with placebo, after exposure to the heat/capsaicin model of cutaneous sensitization. Additionally we are going to assess changes in mood/affect and cognitive function of subjects following administration of fenobam and after cutaneous sensitization compared to baseline.

开始日期2014-01-01

申办/合作机构

Washington University School of Medicine

NCT01806415 / Completed临床1期IIT

A Double Blind, Randomized, Single Dose, Placebo Controlled Study of the Pharmacokinetics and Side Effects of the mGlu5 Antagonist Fenobam in Adult Healthy Volunteers

This is a randomized, blinded, parallel group, placebo-controlled trial on 32 evaluable healthy male and non-pregnant female, 18-50 year old volunteers. The investigators goal is to observe the pharmacokinetics of fenobam after oral administration of 50, 100 or 150 mg in groups of healthy individuals and to compare the side effects and tolerability of a single dose of fenobam with placebo.

开始日期2013-05-01

申办/合作机构

Washington University School of Medicine

NCT00637221 / Completed临床1/2期

An Open Label Exploratory Study to Investigate the Safety and Effects of NPL-2009 ( 50 mg - 150 mg Single Dose) on Prepulse Inhibition Tests and Continuous Performance Tasks, in Adults With Fragile X Syndrome

This is an open label exploratory study to investigate the safety and effects of a single dose of NPL-2009(50 mg - 150 mg) on Prepulse Inhibition (PPI) Tests and Continuous Performance Tasks (CPT) in adults with Fragile X Syndrome

开始日期2008-03-01

申办/合作机构

NeuroPharm, Inc.

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100 项与非诺班相关的转化医学

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100 项与非诺班相关的专利（医药）

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项与非诺班相关的文献（医药）

2024-08-01·Experimental Neurology

Fenobam modulates distinct electrophysiological mechanisms for regulating excessive gamma oscillations in the striatum of dyskinetic rats

Article

作者: Dai, Weina ; Wang, Pengfei ; Xu, Yuming ; Liu, Hongbin ; Liu, Han

Gamma oscillations have been frequently observed in levodopa-induced dyskinesia (LID), manifest as broadband (60-120 Hz) and narrowband (80-110 Hz) gamma activity in cortico-striatal projection. We investigated the electrophysiological mechanisms and correlation of gamma oscillations with dyskinesia severity, while assessing the administration of fenobam, a selective metabotropic glutamate receptor 5 (mGluR5) antagonist, in regulating dyskinesia-associated gamma activity. We conducted simultaneous electrophysiological recordings in Striatum (Str) and primary motor cortex (M1), together with Abnormal Involuntary Movement Scale scoring (AIMs). Phase-amplitude coupling (PAC), power, coherence, and Granger causality analyses were conducted for electrophysiological data. The findings demonstrated increased beta oscillations with directionality from M1 to Str in parkinsonian state. During on-state dyskinesia, elevated broadband gamma activity was modulated by the phase of theta activity in Str, while M1 → Str gamma causality mediated narrowband gamma oscillations in Str. Striatal gamma power (both periodic and aperiodic power), periodic power, peak frequency, and PAC at 80 min (corresponding to the peak dyskinesia) after repeated levodopa injections across recording days (day 30, 33, 36, 39, and 42) increased progressively, correlating with total AIMs. Additionally, a time-dependent parabolic trend of PAC, peak frequency and gamma power was observed after levodopa injection on day 42 from 20 to 120 min, which also correlated with corresponding AIMs. Fenobam effectively alleviates dyskinesia, suppresses enhanced gamma oscillations in the M1-Str directionality, and reduces PAC in Str. The temporal characteristics of gamma oscillations provide parameters for classifying LID severity. Antagonizing striatal mGluR5, a promising therapeutic target for dyskinesia, exerts its effects by modulating gamma activity.

2024-04-01·Heliyon

The protective effects of methylene blue on astrocytic swelling after cerebral ischemia-reperfusion injuries are mediated by Aquaporin-4 and metabotropic glutamate receptor 5 activation

Article

作者: Fan, Yuzhu ; Lai, Yu ; Zhang, Song ; Liu, Xinyan ; Sun, Kan ; Wang, Chunliang ; Han, Jie ; Qiu, Dongxian

Methylene blue (MB) was found to exert neuroprotective effect on different brain diseases, such as ischemic stroke. This study assessed the MB effects on ischemia induced brain edema and its role in the inhibition of aquaporin 4 (AQP4) and metabotropic glutamate receptor 5 (mGluR5) expression. Rats were exposed 1 h transient middle cerebral artery occlusion (tMCAO), and MB was injected intravenously following reperfusion (3 mg/kg). Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed 48 h after the onset of tMCAO to evaluate the brain infarction and edema. Brain tissues injuries as well as the glial fibrillary acidic protein (GFAP), AQP4 and mGluR5 expressions were detected. Oxygen and glucose deprivation/reoxygenation (OGD/R) was performed on primary astrocytes (ASTs) to induce cell swelling. MB was administered at the beginning of reoxygenation, and the perimeter of ASTs was measured by GFAP immunofluorescent staining. 3,5-dihydroxyphenylglycine (DHPG) and fenobam were given at 24 h before OGD to examine their effects on MB functions on AST swelling and AQP4 expression. MB remarkably decreased the volumes of T2WI and ADC lesions, as well as the cerebral swelling. Consistently, MB treatment significantly decreased GFAP, mGluR5 and AQP4 expression at 48 h after stroke. In the cultivated primary ASTs, OGD/R and DHPG significantly increased ASTs volume as well as AQP4 expression, which was reversed by MB and fenobam treatment. The obtained results highlight that MB decreases the post-ischemic brain swelling by regulating the activation of AQP4 and mGluR5, suggesting potential applications of MB on clinical ischemic stroke treatment.

2024-01-04·Brain

Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity

Article

作者: Talhada, Daniela ; Hakon, Jakob ; Nicoletti, Ferdinando ; Englund, Elisabet ; Mastroiacovo, Federica ; Olsson, Roger ; Bauer, Adam Q ; Wieloch, Tadeusz ; Kim, Byungchan ; Moyanova, Slavianka ; Sjölund, Carin ; Quattromani, Miriana J ; Di Menna, Luisa ; Ruscher, Karsten

AbstractStroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischaemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections. The type-5 metabotropic glutamate receptor (mGluR5) has been shown to modulate brain plasticity and function and is a therapeutic target in neurological diseases outside of stroke. We investigated whether mGluR5 influences functional recovery and network reorganization rodent models of focal ischaemia.Using multiple behavioural tests, we observed that treatment with negative allosteric modulators (NAMs) of mGluR5 (MTEP, fenobam and AFQ056) for 12 days, starting 2 or 10 days after stroke, restored lost sensorimotor functions, without diminishing infarct size. Recovery was evident within hours after initiation of treatment and progressed over the subsequent 12 days. Recovery was prevented by activation of mGluR5 with the positive allosteric modulator VU0360172 and accelerated in mGluR5 knock-out mice compared with wild-type mice. After stroke, multisensory stimulation by enriched environments enhanced recovery, a result prevented by VU0360172, implying a role of mGluR5 in enriched environment-mediated recovery. Additionally, MTEP treatment in conjunction with enriched environment housing provided an additive recovery enhancement compared to either MTEP or enriched environment alone. Using optical intrinsic signal imaging, we observed brain-wide disruptions in resting-state functional connectivity after stroke that were prevented by mGluR5 inhibition in distinct areas of contralesional sensorimotor and bilateral visual cortices. The levels of mGluR5 protein in mice and in tissue samples of stroke patients were unchanged after stroke.We conclude that neuronal circuitry subserving sensorimotor function after stroke is depressed by a mGluR5-dependent maladaptive plasticity mechanism that can be restored by mGluR5 inhibition. Post-acute stroke treatment with mGluR5 NAMs combined with rehabilitative training may represent a novel post-acute stroke therapy.

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