Pentylenetetrazol (50 mg/mL) was administered at a dose rate of 40 mg/kg/h by intravenous (IV) infusion at a rate of 10 mL/h in twelve (12) monkeys, until convulsion onset and the infusion was stopped immediately. Diazepam (Sandoz, Boucherville,

QC, Canada; Everolimus research buy 1.0 mg/kg) was administered IV at seizure onset. A caffeine challenge was conducted using a prospective, randomized, controlled, crossover study to illustrate applications of qEEG in drug development. Caffeine (10 mg/kg, IM) was administered approximately 10 min prior to lights off to ten (10) animals (i.e. at 18:00). Sterile saline USP was administered as a control. A wash-out of at least 3 days was allowed between each treatment. Pentylenetetrazol (50 mg/mL) was administered at a dose rate of 100 mg/kg/h by IV infusion to five (5) dogs, until the start of convulsions and was then stopped immediately. Diazepam (1 mg/kg,

IV) was administered immediately following seizure onset. Both EEG and EMG were recorded following saline IV infusion in rats (n = 49) Autophagy Compound Library price or IV PTZ infusion (cross over design with n = 8). Three (3) rats were used to illustrate qEEG effects of diazepam (3 mg/kg, IM) and amphetamine (3.75 mg/kg, PO). Twenty-four (24) rats received a PTZ (8 mg/mL) IV infusion at a dose rate of 288 mg/kg/h. Diazepam (2–6 mg/kg) was administered by intra-peritoneal (IP) injection following tonic convulsion onset. – Sixteen (16) Sprague–Dawley rats were used to illustrate the effect of yohimbine (18 mg/kg, SC, 8 min prior to PTZ infusion) as a positive control (n = 8) in the PTZ seizure threshold model, with an equal number of animals (n = 8) receiving either yohimbine or saline (control). The EEG and EMG (when applicable) traces were analyzed using manual and

automated detection (NeuroScore, Data Science International, St.-Paul, MN, USA). Spectral analysis was performed on 60-s epochs to quantify the absolute and relative amplitude of EEG frequency bands (delta [0.5–4 Hz], theta [4–8 Hz], alpha [8–12 Hz], sigma [12–16 Hz], beta [16–24 Hz] and gamma [24–50 Hz]) and individual frequencies [0.5–127 Hz]. For each parameter, a one-way analysis-of-variance (ANOVA) was conducted and the residuals were saved. Gaussian distribution was evaluated using the Astemizole Shapiro–Wilk test on residuals. Whenever the Shapiro–Wilk test was found to be significant (p ≤ 0.001) then the data were transformed and re-submitted to the analysis. The Levene test was used to examine the homogeneity of group variances. For the ANOVA model, if the overall group differences were shown significant (F-Test), then pair-wise comparisons were conducted using Tukey’s test. Data are presented as mean (SD). The EEG and EMG (when applicable) electrodes were well tolerated in all animals. Premonitory seizure signs observed during the pre-ictal period with associated average PTZ doses are listed in Table 1. Emesis and decreased activity were the most common clinical signs followed by hypersalivation and ataxia.