(1S, 3S)-3-Amino-4-difluoromethylenyl-1-cyclopentanoic Acid (CPP-115), a Potent γ-Aminobutyric Acid Aminotransferase Inactivator for the Treatment of Cocaine Addiction

Pan, Yue; Gerasimov, Madina R.; Kvist, Trine; Wellendorph, Petrine; Madsen, Karsten K.; Pera, Elena; Lee, Hyunbeom; Schousboe, Arne; Chebib, Mary; Bräuner‐Osborne, Hans; Craft, Cheryl M.; Brodie, Jonathan D.; Schiffer, Wynne K.; Dewey, Stephen L.; Miller, Steven R.; Silverman, Richard B.

doi:10.1021/jm201231w

Cited by 44 publications

(69 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Carisbamate has since been granted orphan drug status for IS by the Food and Drug Administration (FDA). Another promising drug is CPP-115, a vigabatrin analog with high affinity for GABA aminotransferase that has shown lower retinal toxicity than vigabatrin (Pan et al 2012; Silverman 2012). CPP-115 reduced spasms in the multiple-hit model showing better efficacy / tolerability profile than vigabatrin, at doses 400 times lower than vigabatrin (Briggs et al 2014).…”

Section: West Syndrome and Infantile Spasmsmentioning

confidence: 99%

Pathogenesis and new candidate treatments for infantile spasms and early life epileptic encephalopathies: A view from preclinical studies

Galanopoulou

Moshé

2015

Neurobiology of Disease

View full text Add to dashboard Cite

Early onset and infantile epileptic encephalopathies (EIEEs) are usually associated with medically intractable or difficult to treat epileptic seizures and prominent cognitive, neurodevelopmental and behavioral consequences. EIEEs have numerous etiologies that contribute to the inter- and intra-syndromic phenotypic variability. Etiologies include structural and metabolic or genetic etiologies although a significant percentage is of unknown cause. The need to better understand their pathogenic mechanisms and identify better therapies has driven the development of animal models of EIEEs. Several rodent models of infantile spasms have emerged that recapitulate various aspects of the disease. The acute models manifest epileptic spasms after induction and include the NMDA rat model, the NMDA model with prior prenatal betamethasone or perinatal stress exposure, and the γ-butyrolactone induced spasms in a mouse model of Down syndrome. The chronic models include the tetrodotoxin rat model, the aristaless related homeobox X-linked (Arx) mouse models and the multiple-hit rat model of infantile spasms. We will discuss the main features and findings from these models on target mechanisms and emerging therapies. Genetic models have also provided interesting data on the pathogenesis of Dravet syndrome and proposed new therapies for testing. The genetic associations of many of the EIEEs have also been tested in rodent models as to their pathogenicity. Finally, several models have tested the impact of subclinical epileptiform discharges on brain function. The impact of these advances in animal modeling for therapy development will be discussed.

show abstract

Section: West Syndrome and Infantile Spasmsmentioning

confidence: 99%

Pathogenesis and new candidate treatments for infantile spasms and early life epileptic encephalopathies: A view from preclinical studies

Galanopoulou

Moshé

2015

Neurobiology of Disease

View full text Add to dashboard Cite

show abstract

“…[intraperitoneally], PN4 -13), but transiently respond to vigabatrin (Scantlebury et al 2010), whereas, appropriately for IS, do not respond to phenytoin (Table 4) . Further confirming the responsiveness to vigabatrin, a recently developed high-affinity inactivator of GABA aminotransferase, CPP-115 (Catalyst Pharmaceutical Partners, Coral Gables, FL), which shows lower than vigabatrin risk for retinal toxicity in animal studies (Pan et al 2012;Silverman 2012), showed better efficacy/tolerability profile in the multiple-hit model (Briggs et al 2014).…”

Section: Animal Models Of Early-life Epilepsymentioning

confidence: 87%

Neonatal and Infantile Epilepsy: Acquired and Genetic Models

Galanopoulou

Moshé

2015

Cold Spring Harb Perspect Med

View full text Add to dashboard Cite

The incidence of seizures and epilepsies is particularly high during the neonatal and infantile periods. We will review selected animal models of early-life epileptic encephalopathies that have addressed the dyscognitive features of frequent interictal spikes, the pathogenesis and treatments of infantile spasms (IS) or Dravet syndrome, disorders with mammalian target of rapamycin (mTOR) dysregulation, and selected early-life epilepsies with genetic defects. Potentially pathogenic mechanisms in these conditions include interneuronopathies in IS or Dravet syndrome and mTOR dysregulation in brain malformations, tuberous sclerosis, and related genetic disorders, or IS of acquired etiology. These models start to generate the first therapeutic drugs, which have been specifically developed in immature animals. However, there are challenges in translating preclinical discoveries into clinically relevant findings. The advances made so far hold promise that the new insights may potentially have curative or disease-modifying potential for many of these devastating conditions. T he neonatal and infantile periods show relatively high age-adjusted incidence of epilepsy compared with other ages of life (Hauser et al. 1993). The etiology of newly diagnosed epilepsies at these ages also is distinct, showing greater representation of epilepsies of unknown, genetic, or congenital etiologies (Hauser et al. 1993). The semiology and syndromic phenotypes of epilepsies that first appear in this early life period are also distinct and often more fulminant, appearing with evident neurodevelopmental problems or regression (e.g., epileptic encephalopathies) or characteristic seizure types (e.g., infantile spasms [IS], multifocal clonic seizures) ( Table 1). In addition, the treatments for epilepsies of these age groups can be specialized, as is the case with the use of hormonal therapies (e.g., adrenocorticotropic hormone [ACTH] in certain epileptic encephalopathies). Given the serious repercussions for the development of these neonates and infants and the importance of finding better therapies with disease-modifying potential, several efforts have been made to create animal models of these conditions to increase our understanding and ability to treat them. Here, we will review selected animal models, genetic or induced, that address epilepsies and epileptic encephalopathies characteristic of neonates and infants.

show abstract

“…A novel GABA-AT inhibitor with increased effectiveness at lower doses and greater target specificity, CPP-115 displays superior enzyme inactivation in comparison to GVG [115]. This medication is currently under Phase II investigation for treatment of cocaine use disorders.…”

Section: Vigabatrin and Its Analoguesmentioning

confidence: 99%

Emerging drugs for the treatment of cocaine use disorder: a review of neurobiological targets and pharmacotherapy

Shorter

Domingo

Kosten

2014

Expert Opinion on Emerging Drugs

View full text Add to dashboard Cite

Research into cocaine pharmacotherapy must continue to show innovation. Given that medications targeting single neurotransmitter systems have demonstrated little efficacy in treatment of cocaine use disorder, the recent focus on pharmacotherapeutic agents with multiple neurobiochemical targets represents an exciting shift in trial design and approach. Additionally, consideration of pharmacogenetics may be helpful in identification of subpopulations of cocaine-dependent individuals who may preferentially respond to medications.

show abstract

(1S, 3S)-3-Amino-4-difluoromethylenyl-1-cyclopentanoic Acid (CPP-115), a Potent γ-Aminobutyric Acid Aminotransferase Inactivator for the Treatment of Cocaine Addiction

Cited by 44 publications

References 46 publications

Pathogenesis and new candidate treatments for infantile spasms and early life epileptic encephalopathies: A view from preclinical studies

Pathogenesis and new candidate treatments for infantile spasms and early life epileptic encephalopathies: A view from preclinical studies

Neonatal and Infantile Epilepsy: Acquired and Genetic Models

Emerging drugs for the treatment of cocaine use disorder: a review of neurobiological targets and pharmacotherapy

Contact Info

Product

Resources

About