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Functional activity of N-methyl-D-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although D-serine is a more potent agonist. Localizations of D-serine and it biosynthetic enzyme serine racemase approximate the distribution of NMDA receptors more closely than(More)
Memantine has been demonstrated to be safe and effective in the symptomatic treatment of Alzheimer's disease (AD). While the neurobiological basis for the therapeutic activity of memantine is not fully understood, the drug is not a cholinesterase inhibitor and, therefore, acts differently from current AD therapies. Memantine can interact with a variety of(More)
1. The direct activation of the GABAA receptor by pentobarbitone (PB) and phenobarbitone (PHB) was characterized in cultured rat hippocampal neurons using whole-cell voltage clamp and single channel recording techniques. 2. In whole-cell recordings, PB and PHB produced a concentration-dependent activation of Cl- current (EC50 values, 0.33 and 3.0 mM,(More)
Prolonged low-frequency stimulation of excitatory afferents to basolateral amygdala neurons results in enduring enhancement of excitatory synaptic responses. The induction of this form of synaptic plasticity is eliminated by selective antagonists of GluR5 kainate receptors and can be mimicked by the GluR5 agonist ATPA. Kainate receptor-mediated synaptic(More)
Certain neurosteroids rapidly alter the excitability of neurons, in part by potentiating gamma-aminobutyric acid (GABA)-evoked chloride currents, and, like other GABA potentiating drugs, may have anticonvulsant activity. We compared the abilities of a series of isomeric metabolites of progesterone and deoxycorticosterone (3-hydroxy pregnane-20-ones and(More)
Stress affects seizure susceptibility in animals and humans, but the underlying mechanisms are obscure. Here, we provide evidence that GABA(A) receptor-modulating neurosteroids derived from deoxycorticosterone (DOC) play a role in stress-related changes in seizure control. DOC, an adrenal steroid whose synthesis is enhanced during stress, undergoes(More)
Antiepileptic drugs (AEDs) are commonly prescribed for nonepileptic conditions, including migraine headache, chronic neuropathic pain, mood disorders, schizophrenia and various neuromuscular syndromes. In many of these conditions, as in epilepsy, the drugs act by modifying the excitability of nerve (or muscle) through effects on voltage-gated sodium and(More)
The ketogenic diet is a valuable therapeutic approach for epilepsy, one in which most clinical experience has been with children. Although the mechanism by which the diet protects against seizures is unknown, there is evidence that it causes effects on intermediary metabolism that influence the dynamics of the major inhibitory and excitatory(More)
Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnane-20-one), an orally active synthetic analog of the neuroactive steroid allopregnanolone, is a positive allosteric modulator of gamma-aminobutyric acid(A) receptors with anticonvulsant properties. We sought to determine whether tolerance occurs to the anticonvulsant activity of ganaxolone in the(More)