A Randomized, Double-Blind, Placebo-Controlled, Dose-Titration Study to Assess the Safety, Tolerability, and Efficacy of C105 in Persons With Multiple Sclerosis With Cognitive Impairment

The purpose of this study is to determine the safety and efficacy of C105 in treating the cognitive deficits that can occur due to multiple sclerosis.

开始日期2006-11-01

申办/合作机构

Cognition Pharmaceuticals, LLC

100 项与 Levoamphetamine 相关的临床结果

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100 项与 Levoamphetamine 相关的转化医学

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100 项与 Levoamphetamine 相关的专利（医药）

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763

项与 Levoamphetamine 相关的文献（医药）

2023-12-01·Journal of Psychopharmacology

Hyperdopaminergia in rats is associated with reverse effort-cost dependent performance

Article

作者: Savchenko, Artem ; Leo, Damiana ; Sukhanov, Ilya ; Belozertseva, Irina

Background: Dopamine is implicated in the effort-based control of motivational processes; however, whether tonic dopamine regulates the effort-cost impact on motivation, is still debated. Aims: The rats lacking the dopamine transporter (DAT), which have dramatically increased levels of the synaptic dopamine, were used in the present study to elucidate the role of the synaptic dopamine in motivational processes. Methods: To study the reward-related processes, the progressive ratio 3 (PR3) operant schedule of food reinforcement (the ratio increases by 3 after each earned reinforcer) was performed in adult male rats (DAT knockouts (DAT-KO), heterozygotes (DAT-HT) and wild-types (DAT-WT)). Results: During the PR3 session, the response rate of DAT-KO rats was gradually increased following the augmented required number of responses. In contrast, the local response rate of DAT-WT and DAT-HT decreased. d-Amphetamine sulfate salt (3 mg/kg, i.p.) altered the local response rate dynamics in DAT-WT, which became similar to that of DAT-KO. Interestingly, the reduction in response rate at low effort demands was associated with decreased rate of entries into the magazine tray in DAT-WT rats treated with amphetamine (3 mg/kg) but not in DAT-KO rats. Conclusions: Our results suggest that the elevated tonic synaptic dopamine can strongly affect motivation/effort-cost relation in rodents.

2023-11-01·JHEP Reports

The novel cyclophilin inhibitor C105SR reduces hepatic ischaemia–reperfusion injury via mitoprotection

Article

作者: Ahnou, Nazim ; Morin, Didier ; Ahmed-Belkacem, Abdelhakim ; Teixeira-Clerc, Fatima ; Kheyar, Amel ; Guichou, Jean-François ; Pawlotsky, Jean-Michel ; Hulin, Anne ; Ghaleh, Bijan ; Pressiat, Claire

Background & AimsMitochondrial permeability transition pore (mPTP) opening is critical for mediating cell death during hepatic ischaemia-reperfusion injury (IRI). Blocking mPTP opening by inhibiting cyclophilin D (CypD) is a promising pharmacological approach for the treatment of IRI. Here, we show that diastereoisomers of a new class of small-molecule cyclophilin inhibitors (SMCypIs) have properties that make them attractive candidates for the development of therapeutic agents against liver IRI.MethodsDerivatives of the parent SMCypI were synthesised and evaluated for their ability to inhibit CypD peptidyl-prolyl cis-trans isomerase (PPIase) activity and for their mitoprotective properties, evaluated by measuring mitochondrial swelling and calcium retention capacity in liver mitochondria. The ability of the selected compounds to inhibit mPTP opening was evaluated in cells subjected to hypoxia/reoxygenation using a calcein/cobalt assay. Their ability to inhibit cell death was evaluated in cells subjected to hypoxia/reoxygenation by measuring lactate dehydrogenase (LDH) release, propidium iodide staining, and cell viability. The compound performing best in vitro was selected for in vivo efficacy evaluation in a mouse model of hepatic IRI.ResultsThe two compounds that showed the strongest inhibition of CypD PPIase activity and mPTP opening, C105 and C110, were selected. Their SR diastereoisomers carried the activity of the racemic mixture and exhibited mitoprotective properties superior to those of the known macrocyclic cyclophilin inhibitors cyclosporin A and alisporivir. C105SR was more potent than C110SR in inhibiting mPTP opening and prevented cell death in a model of hypoxia/reoxygenation. Finally, C105SR substantially protected against hepatic IRI in vivo by reducing hepatocyte necrosis and apoptosis.ConclusionsWe identified a novel cyclophilin inhibitor with strong mitoprotective properties both in vitro and in vivo that represents a promising candidate for cellular protection in hepatic IRI.Impact and ImplicationsHepatic ischaemia-reperfusion injury (IRI) is one of the main causes of morbidity and mortality during or after liver surgery. However, no effective therapies are available to prevent or treat this devastating syndrome. An attractive strategy to prevent hepatic IRI aims at reducing cell death by targeting mitochondrial permeability transition pore opening, a phenomenon regulated by cyclophilin D. Here, we identified a new small-molecule cyclophilin inhibitor, and demonstrated the enhanced mitoprotective and hepatoprotective properties of one of its diastereoisomers both in vitro and in vivo, making it an attractive lead compound for subsequent clinical development.

2022-10-01·EFSA Journal

Safety and efficacy of a feed additive consisting of l‐lysine monohydrochloride and l‐lysine sulfate produced by fermentation with Corynebacterium glutamicum CGMCC 17927 for all animal species (Barentz Animal Nutrition B.V.)

Article

作者: Lopez-Alonso, Marta ; Villa, Roberto Edoardo ; Petkova, Mariana ; Galobart, Jaume ; Ramos, Fernando ; Ortuno Casanova, Jordi ; Marcon, Francesca ; Brozzi, Rosella ; Fasmon Durjava, Mojca ; Lopez Puente, Secundino ; EFSA Panel on Additives and Products or Substances used in Animal Feed ; de Lourdes Bastos, Maria ; Garcia Cazorla, Yolanda ; Anguita, Montserrat ; Azimonti, Giovanna ; Sanz, Yolanda ; Woutersen, Ruud ; Firmino, Joana ; Dusemund, Birgit ; Revez, Joana ; Bampidis, Vasileios ; Christensen, Henrik ; Tarres-Call, Jordi ; Mayo, Baltasar ; Pettenati, Elisa ; Pechova, Alena ; Kouba, Maryline

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on l-lysine monohydrochloride and l-lysine sulfate produced by Corynebacterium glutamicum CGMCC 17927, when used as a nutritional additive in feed and water for drinking for all animal species. The active substance is l-lysine, and it was produced in two different forms: monohydrochloride (HCl) or sulfate salts. The production strain was genetically modified. Neither viable cells nor recombinant DNA of the production strain were detected in the final products. Therefore, the Panel concluded that the additives did not pose any safety concern regarding the production strain. The use of l-lysine HCl and l-lysine sulfate produced by the strain C. glutamicum CGMCC 17927 in supplementing feed to compensate for l-lysine deficiency in feedingstuffs was safe for the target species. The FEEDAP Panel identified risks of nutritional imbalances and hygienic concerns for amino acids when administered simultaneously in feed and in water for drinking. The use of both forms of l-lysine produced by fermentation using C. glutamicum CGMCC 17927 in animal nutrition was considered safe for the consumers and for the environment. Exposure of users through inhalation to l-lysine HCl and l-lysine sulfate produced with C. glutamicum CGMCC 17927 was considered very likely. In absence of data, the FEEDAP Panel could not conclude on the potential of both forms of the additive to be irritant for skin and eyes or to be dermal sensitisers. l-Lysine HCl and l-lysine sulfate were considered as efficacious sources of the essential amino acid l-lysine for non-ruminant animal species. For the supplemental l-lysine to be as efficacious in ruminants as in non-ruminant species, it would require protection against degradation in the rumen.

100 项与 Levoamphetamine 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	Levoamphetamine	-	-

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
认知功能障碍	临床2期	美国	Cognition Pharmaceuticals, LLC	2006-11-01
多发性硬化症	临床2期	美国	Cognition Pharmaceuticals, LLC	2006-11-01
认知障碍	临床2期	-	Brown University	-
认知障碍	临床2期	-	Mithridion, Inc.	-