Modulation of the epileptic seizure threshold: implications of biphasic dose responses.
Considerable evidence has emerged that hormetic-like biphasic dose-response relationships are common in the biomedical sciences. Consequently, this article assesses dose-response relationships of agents known to modulate epileptic-like seizure thresholds in screening tests with animal models. Biphasic dose responses have been commonly reported as measured by changes in seizure threshold concentrations across a broad dose-response continuum of chemically diverse agents that act via different receptor-based mechanisms. Despite such differences in chemical structure and modes of actions, the quantitative features of these dose responses are quite similar, being consistent with the hormetic dose-response model with respect to the magnitude and width of the stimulatory responses. The hormetic responses were also independent of the animal model employed as well as type of seizure-related endpoint measured. These findings support the generalizability of the hormetic dose-response concept and may have important implications for the discovery of antiseizure drugs and their clinical evaluation.
Calabrese
Edward J
EJ
Department of Public Health, School of Public Health and Health Sciences, Environmental Health Sciences Divison, University of Massachusetts, Amherst, Massachusetts 01003, USA. edwardc@schoolph.umass.edu
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003292:Convulsants; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D051379:Mice; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*
D000927:Anticonvulsants; D003292:Convulsants