Michael W. Hill

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The diazoxide derivative 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine-S,S-dioxide (IDRA21) enhances memory and learning in rodents, most likely by potentiating AMPAergic synaptic activity. We examined IDRA21's effect upon AMPAergic synaptic currents and whole-cell glutamate currents in cultured rat hippocampal neurons to determine whether IDRA21(More)
PURPOSE As a preliminary step in the development of an implantable Peltier device to abort focal neocortical seizures in vivo, we have examined the effect of rapid cooling on seizures in rodent hippocampal-entorhinal slices. METHODS Seizure-like discharges were induced by exposing the slices to extracellular saline containing 4-aminopyridine (50(More)
The time course of EPSCs and IPSCs is at least partly determined by the concentration profile of neurotransmitter acting on postsynaptic receptors. Several recent reports have suggested that the peak synaptic cleft concentration of the inhibitory neurotransmitter GABA likely reaches at least 500 microM, a level that saturates the GABAA receptor. In the(More)
A series of 3-substituted 2-piperidinone (delta-valerolactam) and hexahydro-2H-azepin-2-one (epsilon-caprolactam) derivatives were prepared and evaluated as anticonvulsants in mice. In the 2-piperidinone series, 3,3-diethyl compound 7b is the most effective anticonvulsant against pentylenetetrazole-induced seizures (ED50, 37 mg/kg; PI (TD50/ED50), 4.46),(More)
3-Benzyl-3-ethyl-2-piperidinone (3-BEP) belongs to a family of compounds that includes alpha- substituted gamma-butyrolactones, gamma-thiobutyrolactones, 2-pyrrolidinones and hexahydro-2H-azepin-2-ones. Many of these drugs exhibit potent in vivo anticonvulsant activity in mice. Previous electrophysiological studies demonstrated that they potentiate(More)
Some 3,3-disubstituted 2-pyrrolidinones and 2-piperidinones (five- and six-membered ring lactams, respectively) possess potent in vivo anticonvulsant activity. In vitro these lactams potentiate GABA(A) receptor-mediated chloride currents, which is thought to be the mechanism by which they exert their therapeutic effects. However, the apparent affinity for(More)
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