Timothy E. Albertson

Neuropharmacology methods in epilepsy research

Electroshock, Steven L. Peterson Chemoconvulsants, H. Steve White The Kindling Model of Temporal Lobe Epilepsy, Mary Ellen Kelly Rapid Kindling: Behavioral and Electrographic, Janet L. Stringer Experimental Models of Status Epilepticus, Jeffery H. Goodman Audiogenic Seizures in Mice and Rats, Charles E. Reigel Models of Focal Epilepsy in Rodents, Charles R. Craig Evaluation of Associated Behavioral and Cognitive Deficits in Anticonvulsant Drug Testing, Piotr Wlaz and Wolfgang Loscher Gene Targeting Models of Epilepsy: Technical and Analytical Considerations, Laurence H. Tecott The Hippocampal Slice Preparation, Larry G. Stark and Timothy E. Albertson Microdialysis Techniques for Epilepsy Research, John W. Dailey and Pravin K. Mishra Methodologies for Determining Rhythmic Expression of Seizures, Thomas H. Champney Index

Pharmacological and Toxicological Evaluation of Potential Antiepileptic Drugs in the Kindling Model of Epilepsy

The history of the pharmacology of antiepileptic drugs is now over 50 years old and much of the pioneering work can be traced to the discovery and development of phenytoin. The history and details of that particular research have recently been summarized and reviewed [7]. The use of pentylenetetrazol to produce chemoshock seizures and the subsequent discovery of trimethadione brought the science of pharmacology into the domain of antiepileptic drug testing in an even more permanent way. Toman, Swinyard, Goodman, Brown, Richards and Everett published a series of papers that further developed and quantified maximal electroshock and pentylenetetrazol models of epilepsy [31,30,29,28,5] that remain key components in the preclinical testing and evaluation of antiepileptic drugs (AEDs). Among this pioneering work one finds constant emphasis on not only refinement of methods useful for detection of antiepileptic drug efficacy, but on estimation of drug selectivity as a very important consideration.

The Salford Lung Study: a pioneering comparative effectiveness approach to COPD and asthma in clinical trials

The Salford Lung Study (SLS) of patients with asthma and chronic obstructive pulmonary disease (COPD) is a practical, community-based, randomized, open-label pragmatic study on the efficacy and safety of the once-daily dry powder inhaler that combines the inhaled corticosteroid fluticasone furoate (FF) with the long-acting beta2 agonist vilanterol (VI). The asthma component of the SLS is not yet reported but the COPD component, done over a 12-month period, found a statistically significant 8.4% reduction in COPD exacerbations when compared to usual care. No differences in adverse events, including serious adverse events and pneumonia, were noted. The importance of real-world findings, such as those found in the SLS COPD trial with inhaled FF/VI, is discussed in comparison to classical randomized controlled trials (RCTs) with inhaled FF/VI in COPD patients. The real-world, community-based pragmatic RCT like the SLS provides additional generalizable data with direct clinical applicability and potential usefulness in the development of practice guidelines. The results from the SLS, along with those of large and small RCTs, are supportive of the use of once-daily FF/VI in COPD maintenance therapy.

INTERACTIONS BETWEEN CONVULSANTS AT LOW-DOSE AND PHENOBARBITAL IN THE HIPPOCAMPAL SLICE PREPARATION'

Our laboratory has had a sustained interest in development and use of animal models of epilepsy, and some of our previous studies were included in the proceedings of the Kindling 4 conference17. One of the reasons the kindling model has been of special interest is because the slow development of the electroencephalographic and behavioral events associated with it provide us with the opportunity to study the transitional events leading to the final kindled state. We have exploited the model from both the pharmacological and the toxicological point of view. On the pharmacological side, we have studied many conventional and novel compounds for their effects on retardation of kindling development, or on fully kindled seizures1,2,11,13 On the toxicological side, we have reported the proconvulsant effects of a number of compounds, including lindane12–14, a chlorinated hydrocarbon insecticide which was previously broadly used throughout the world and is still the principal ingredient in a medicated shampoo. The work to be described is a direct outgrowth and extension of studies previously reported on lindane, and we have sought to compare it with several other convulsants known to interact with the GABA-A receptor-chloride ionophore complex by examining the electrophyiological consequences of exposing hippocampal slices to each of them.