Charles H. Large

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Phencyclidine (PCP), a glutamate/N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to induce a range of symptoms similar to those of patients with schizophrenia, while d-amphetamine induces predominantly positive symptoms. Previous studies in our laboratory have shown that PCP can selectively impair the performance of an operant(More)
The combination of brain stimulation techniques like transcranial magnetic stimulation (TMS) with CNS active drugs in humans now offers a unique opportunity to explore the physiologic effects of these substances in vivo in the human brain. Motor threshold, motor evoked potential size, motor evoked potential intensity curves, cortical silent period,(More)
Lamotrigine, a broad-spectrum anticonvulsant known to block brain sodium channels, is effective in the treatment of persons with bipolar disorder, perhaps by virtue of its ability to reduce glutamate release. Furthermore, lamotrigine decreases the perceptual abnormalities produced by the N-methyl-d-aspartate (NMDA) antagonist ketamine in humans, similar to(More)
Acute administration of NMDA receptor (NMDAR) antagonists such as phencyclidine (PCP) or ketamine induces symptoms that closely resemble those of schizophrenia in humans, a finding that has led to the hypothesis that a decreased NMDAR function may be a predisposing or even causative factor in schizophrenia. However, the precise neuropharmacological(More)
N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine and phencyclidine, induce perceptual abnormalities, psychosis-like symptoms, and mood changes in healthy humans and patients with schizophrenia. The similarity between NMDA receptor antagonist-induced psychosis and schizophrenia has led to the widespread use of the drugs to provide models to(More)
The pharmacologic profile of retigabine [RTG (international nonproprietary name); ezogabine, EZG (U.S. adopted name)], is different from all currently approved antiepileptic drugs (AEDs). Its primary mechanism of action (MoA) as a positive allosteric modulator of KCNQ2-5 (K(v) 7.2-7.5) ion channels defines RTG/EZG as the first neuronal potassium (K(+))(More)
Bipolar disorder is a psychiatric condition characterised by episodes of mania, depression, and underlying mood instability. Anticonvulsant drugs have an established place in the treatment of the disorder, but identifying novel drugs in this class is complicated by the absence of validated animal models. We have evaluated the efficacy of three(More)
Atypical antipsychotic drugs are the drugs of choice for the treatment of schizophrenia. However, despite advances, no treatments have been established for patients who fail to improve with the most effective of these, clozapine. The inhibition of dopamine transmission through blockade of dopamine D2 receptors is considered to be essential for antipsychotic(More)
Retigabine [RTG (international nonproprietary name); ezogabine (EZG; U.S. adopted name)] is a first-in-class antiepileptic drug (AED) that reduces neuronal excitability by enhancing the activity of KCNQ (K(v)7) potassium (K(+)) channels. RTG/EZG has recently been approved by the European Medicines Agency and the U.S. Food and Drug Administration as(More)
Transgenic or knockout mouse models provide the opportunity to study the function of disease-related or novel genes. However, a confounding factor in all such research is the genetic and phenotypic variation of the mouse strain used to construct the models. A trait which is frequently studied in transgenic models of neurological disorders is synaptic(More)