A study conducted by Scaramelli et al. (2009) revealed that 39 out of 100 patients reported premonitory signs, including behavioral this website and cognitive changes, prior to seizure onset. Humans may report confusion prior to a seizure but such a qualitative sign cannot be obtained in animal models other than by careful behavioral evaluations (e.g. disorientation, ataxia). To support interpretation, video recording concomitant to EEG monitoring allows for observation of premonitory signs

of seizure (e.g. salivation, emesis, ataxia, tremors) ( Podell, 2010) that are not otherwise captured by EEG recording alone. In addition, the margin between plasma exposure at onset of premonitory clinical signs, and at seizure onset, can be measured and serves to evaluate the risk associated with the drug candidate. Observation of such premonitory signs in clinical trials will often halt dosing.

The onset of VE-821 purchase adverse effects is unpredictable and restraining an animal for an extended period of time (i.e. several hours) is not feasible or ethical. In fact, restraint has been shown to lower seizure threshold during seizure susceptibility studies ( Swinyard, Radhakrishnan, & Goodman, 1962). Continuous video-EEG monitoring by telemetry can be an alternative to monitor freely moving animals, therefore decreasing the potential for stress-related artifacts or changes in seizure threshold. The current study aimed to present representative EEG results obtained by telemetry combined with video in conscious Beagle dogs, cynomolgus monkeys and Sprague–Dawley rats after determination of the pentylenetetrazol (PTZ)-induced seizure threshold. Our hypothesis was that the Beagle dog would be more sensitive to PTZ both on the seizurogenic dose and premonitory clinical signs determination. Moreover, quantitative EEG spectral changes (qEEG) considered

too as an advanced analysis strategy was undertaken in rats and monkeys to illustrate methodologies to screen for drug-induced stimulatory or neuro-depressive effects. Doses of non-seizurogenic drugs used for qualification of qEEG were selected to induce slight to moderate effects based on historical data (unpublished). These results are discussed in the context of seizure liability study design and interpretation. During the study, care and use of animals were conducted in accordance with principles outlined in the current Guide to the Care and Use of Experimental Animals published by the Canadian Council on Animal Care and the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (National Research Council, 2011). CiToxLAB North America’s facility is AAALAC accredited. All procedures were conducted as per Standard Operating Procedures (SOPs) and with approval and overview of the institutional animal care and use committee.