Phenotypic Assessment and the Discovery of Topiramate

Maryanoff, Bruce E.

doi:10.1021/acsmedchemlett.6b00176

Cited by 21 publications

(19 citation statements)

References 37 publications

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“…In humans, topiramate was introduced as a secondgeneration AED in the early 2000 16 but soon later it was found to be a useful migraine prophylactics and weight loss medication. 17 Its unique structure provides a broad spectrum of antiseizure properties. Topiramate enhances chlorideion currents evoked by γ-aminobutyric acid (GABA) at GABA A receptors, inhibits kainate/alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid-type glutamate receptors, and attenuates voltage-sensitive sodium and calcium channels.…”

Section: Discussionmentioning

confidence: 99%

Idiosyncratic reaction of topiramate in a Maine Coon cat

Du¹,

Draper²

2021

Vet Record Case Reports

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A 1.5‐year‐old Main Coon neutered male cat was presented for cluster epileptic seizures. The cat was first treated with phenobarbital; however, it had to be discontinued due to anticonvulsant hypersensitivity syndrome. Topiramate was then initiated. Shortly thereafter, a persistent neutropenia developed and the topiramate was stopped. The epileptic seizures are now adequately controlled by levetiracetam extended release 500 mg every 12 hours and the neutropenia had resolved. This is the first report of adverse drug reaction of topiramate in cats.

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Section: Discussionmentioning

confidence: 99%

Idiosyncratic reaction of topiramate in a Maine Coon cat

Du¹,

Draper²

2021

Vet Record Case Reports

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“…Topiramate is FDA-approved for treating generalized tonic-clonic and complex partial seizures 17 and for migraine prophylaxis. More recently, it has been used off-label for weight loss in both psychiatric and non-psychiatric patients.…”

Section: Topiramatementioning

confidence: 99%

Managing metabolic syndrome in patients with schizophrenia

Singh¹,

Allen²

2020

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M r. N, age 55, has a long, documented history of schizophrenia.His overall baseline functioning has been poor because he is socially isolated, does not work, and lives in subsidized housing paid for by the county where he lives. His psychosocial circumstances have limited his ability to afford or otherwise obtain nutritious food or participate in any type of regular exercise program. He has been maintained on olanzapine, 20 mg nightly, for the past 5 years. During the past year, his functioning and overall quality of life have declined even further after he was diagnosed with hypertension. Mr. N's in-office blood pressure was 160/95 mm Hg (normal range: systolic blood pressure, 90 to 120 mm Hg, and diastolic blood pressure, 60 to 80 mm Hg). He says his primary care physician informed him that he is pre-diabetic after his hemoglobin A1c came back at 6.0 mg/dL (normal range <5.7 mg/dL) and his body mass index was 32 kg/m 2 (normal range 18.5 to 24.9 kg/m 2 ). Currently, Mr. N's psychiatric symptoms are stable, but his functional decline is now largely driven by metabolic parameters. Along with lifestyle changes and nonpharmacologic interventions, what else should you consider to help him?In addition to positive, negative, and cognitive symptoms, schizophrenia is accompanied by disturbances in metabolism, 1 inflammatory markers, 2 and sleep/wake cycles. 3 Current treatment strategies focus on addressing symptoms and functioning, but the metabolic and inflammatory targets that account for significant morbidity and mortality remain largely unaddressed. Managing metabolic syndrome in patients with schizophrenia

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“…Later, a wave passed through the industry from about the 1970s till the early 2010s which emphasized creating massive combinatorial libraries of compounds and expression of single biomolecular targets (thus mode of action usually predetermined), and assaying them in vitro in high‐throughput screens (HTS), and highly automated systems and data collection/analysis. Now in the last decade, there has been a return to different types of ‘phenotype‐based in vivo screening’ such as on zebrafish, 14,15 various mammals, 16 nematodes 17 etc., including in the search for drugs for neurological diseases which are often extremely difficult to model in vitro 18–22 . Thus in a sense in pharma, ‘what is old is new again’, though current iterations of phenotype‐based discovery are dramatically augmented by genome editing and genetic engineering.…”

Section: Introductionmentioning

confidence: 99%

Pharmaceutical technologies with potential application to insecticide discovery^†

Wing¹

2020

Pest Management Science

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Novel neuroactive insecticides are discovered/registered differently, have a lower value in use, and exert their physiological actions in manners distinct from neuroactive pharmaceuticals, but there are clear similarities in their biochemical modes of action. Insecticides are generally discovered using whole pest insect screens, and this eases difficulties in ‘translational science’ from laboratory to field, as opposed to pharmaceutical translation from biochemical or cell‐based targets to animal models to human clinical trials to registered drug. This paper examines recent trends in pharmaceutical science and identifies some technologies which may represent complementary approaches to insecticide discovery screening and mode of action determination beyond the sound processes in common practice today. Examples will be drawn from nanoparticle delivery of neuroactives, unique ligand–polymer conjugates, proposed advances in insect cell culture following from pharmaceutical cell biology, and laboratory or organ‐on‐a‐chip approaches. It is hoped that these concepts will stimulate novel thinking which may enable discovery of efficacious new neuroactive insecticides. © 2020 Society of Chemical Industry

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Phenotypic Assessment and the Discovery of Topiramate

Abstract: The role of phenotypic assessment in drug discovery is discussed, along with the discovery and development of TOPAMAX (topiramate), a billion-dollar molecule for the treatment of epilepsy and migraine.

Cited by 21 publications

References 37 publications

Idiosyncratic reaction of topiramate in a Maine Coon cat

Idiosyncratic reaction of topiramate in a Maine Coon cat

Managing metabolic syndrome in patients with schizophrenia

Pharmaceutical technologies with potential application to insecticide discovery^†

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Phenotypic Assessment and the Discovery of Topiramate

Abstract: The role of phenotypic assessment in drug discovery is discussed, along with the discovery and development of TOPAMAX (topiramate), a billion-dollar molecule for the treatment of epilepsy and migraine.

Cited by 21 publications

References 37 publications

Idiosyncratic reaction of topiramate in a Maine Coon cat

Idiosyncratic reaction of topiramate in a Maine Coon cat

Managing metabolic syndrome in patients with schizophrenia

Pharmaceutical technologies with potential application to insecticide discovery†

Contact Info

Product

Resources

About

Pharmaceutical technologies with potential application to insecticide discovery^†