Distribution, Metabolism, and Excretion of Cenobamate in Adult, Fetal, Neonatal, and Lactating Rats.

Background And Objective: Cenobamate is an antiseizure medication (ASM) approved for treatment of focal epilepsy in adults. The objective of this study was to characterize the distribution, metabolism, and excretion of cenobamate in adult and pre- and postnatal rats, including pregnant and lactating females and nursing pups.

Methods: Distribution, metabolic, and excretion profiles were determined for C-labeled and unlabeled cenobamate using liquid scintillation counting, radiochromatography, LCMS, and LCMS/MS after oral or intravenous (IV) administration.

Anticonvulsant effects of cenobamate in chemically and electrically induced seizure models in rodents.

Background: Cenobamate is an antiseizure medication used to treat partial-onset (focal) seizures. It is a molecule with one chiral center and a unique dual mechanism of action: enhancement of fast and slow inactivation of sodium channels with preferential inhibition of the persistent current and positive allosteric modulation of GABA receptor-mediated ion channels.

Aims/methods: Anticonvulsant effects of cenobamate (YKP3089; R-enantiomer), YKP3090 (S-enantiomer), and YKP1983 (racemate) were evaluated in chemically and electrically induced focal and generalized seizure models in rodents.

Positive allosteric modulation of GABA receptors by a novel antiepileptic drug cenobamate.

Cenobamate is a novel antiepileptic drug under investigation for use in patients with focal (partial-onset) seizures. To understand its potential molecular mechanism of action, the effects of cenobamate on GABA-mediated currents and GABA receptors in rodent hippocampal neurons were examined. Cenobamate potentiated GABA-induced currents (I) in acutely isolated CA3 pyramidal cells in a concentration-dependent manner (EC, 164 μM), which was not affected by flumazenil, a benzodiazepine receptor antagonist.

Mass Balance, Metabolism, and Excretion of Cenobamate, a New Antiepileptic Drug, After a Single Oral Administration in Healthy Male Subjects.

Background And Objective: Cenobamate is an antiepileptic drug for the treatment of partial-onset seizures. The current study was designed to assess the mass balance and the metabolic profiling of cenobamate in humans.

Methods: Absorption, metabolism, and excretion of cenobamate were investigated in healthy male subjects after a single oral dose of 400 mg of cenobamate containing 50 µCi of [C]-cenobamate as capsule formulation.

Standardization of a novel blood-sampling method through the jugular vein for use in the quantified [14C] 2-deoxyglucose method.

In the traditional [14C] deoxyglucose (2DG) method for the measurement of local cerebral glucose utilization (LCGU), blood samples are collected from the femoral artery. However, the placement of a femoral catheter can affect locomotor activity of the animal. We wanted to develop a new technique for blood sampling that would not interfere with the ongoing behavior.

Perinatal AZT exposure alters the acoustic and tactile startle response to 8-OH-DPAT and apomorphine in adult rats.

The present study was designed to assess the dopaminergic and serotonergic contributions of the acoustic startle response (ASR) and the tactile startle response (TSR) in adult rats that had been perinatally exposed to AZT (azidothymidine, zidovudine; an antiretroviral agent). Each dam was randomly assigned to a treatment group: non-treated, AZT0, 100 or 150 mg/kg. Once daily gastric intubation began prenatally on gestational day (G) 19 and continued to G22 and then the pups were intubated between postnatal day (PND) 2-20.

Preweaning cocaine exposure alters brain glucose metabolic rates following repeated amphetamine administration in the adult rat.

Developmental cocaine exposure produces long-term alterations in function of many neuronal circuits. This study examined glucose metabolic rates following repeated amphetamine administration in adult male and female rats pretreated with cocaine during postnatal days (PND) 11-20. PND11-20 cocaine increased the response to amphetamine in many components of the motor system and the dorsal caudate-putamen, in particular, and decreased the metabolic response in the hypothalamus.

Correlating brain metabolism with stereotypic and locomotor behavior.

Many studies have shown that developmental cocaine exposure alters brain function and behavior, the present study examined the relationship between brain metabolism and behavioral responses to drug challenge. SKF 82958, a selective D1 dopamine agonist, was administered to preweaning cocaine-exposed (50 mg/kg/day) rats and controls at 60 days of age. Deoxyglucose was administered 30 min later, during the peak behavioral response, to measure brain functional activity.

Blunted metabolic response to SKF 82958 in the mesolimbic system following preweaning cocaine treatment.

This study examined glucose metabolic rates following dopamine D(1) agonist challenge in adult male rats pretreated with cocaine during postnatal days 11-20. Water-pretreated control rats showed a reliable decrease in glucose metabolism of rostral mesolimbic structures when challenged with SKF 82958 while cocaine-pretreated males did not. These data support the notion that cocaine exposure during the preweaning period dampens D(1) receptor-mediated function and that the mesolimbic system exhibits a selective vulnerability to early cocaine exposure.

The effects of perinatal AZT exposure on the acoustic startle response in adult rats.

AZT (azidothymidine, zidovudine, ZDV) has become the standard medication to prevent the transmission of the human immunodeficiency virus from mother to fetus. The present study was designed to assess the acoustic startle response (ASR) in adult rats that had been perinatally exposed to AZT. Each litter was randomly assigned to a treatment group: nontreated, AZT 0, 50, 100 or 150 mg/kg.

A simple procedure for assessing ataxia in rats: effects of phencyclidine.

The present study describes an objective, cost- and time-efficient procedure for characterizing the ataxic effects of psychoactive drugs. Male Sprague-Dawley rats were administered an intraperitoneal injection of either saline or one of three doses (1, 5 or 10 mg/kg) of phencyclidine (PCP) 15 min prior to being placed into an empty standard operant conditioning chamber (all manipulanda were removed). The floor of the test apparatus consisted of parallel rows of metal rods spaced approximately 1.