RESATORVID

Formulation

The table below describes the formulation of resatorvid and the controls morphine sulfate and gabapentin for the following in vivo experiments.

Experiment(s) Compound Dose(s) mg/kg Correction factor Dose volume mL/kg Route Vehicle Suspension / Solution
Pharmacokinetics Resatorvid 3, 30 1.00 10 SC DMSO / Solution
Tween 80
Irwin, Rotarod Resatorvid 3, 10, 30, 100 1.00 10 SC DMSO / Solution
Tween 80
Plantar incision, Resatorvid 1, 3, 10, 30 1.00 10 SC DMSO / Solution
L5/L6 SNL Tween 80
Plantar incision Morphine 6 1.33 1 SC Saline Solution
L5/L6 SNL Gabapentin 60 1.00 1 PO Saline Solution

L5/L6 SNL = L5/L6 spinal nerve ligation; PO = per os; SC = subcutaneous; DMSO/Tween 80 = 10% dimethylsulfoxide (DMSO), 5% Tween 80, and 85% sterile water


Results

Expand and Collapse accordion content

Method: Protein binding
A table shows the results of rapid equilibrium dialysis (RED) and Centrifree centrifugation assays to assess protein binding and stability of retigabine. In rat plasma in RED, retigabine was 72.9% bound to protein and 27.1% unbound and had a recovery of 74.4%. In rat brain homogenate in RED, retigabine was 39.2% bound to protein and 60.8% unbound and had a recovery of 119.5%. In rat plasma in Centrifree, retigabine was 78.5% bound to protein and 21.5% unbound and had a recovery of 118.4%. In rat brain homogenate in Centrifree, retigabine was 44.2% bound to protein and 55.8% unbound and had a recovery of 128.5%. Acebutolol, quinidine, and warfarin were included in the study as controls and returned values consistent with literature values in both RED and Centrifree assays.

Method: Rotarod Animals were balanced across treatment groups based on body weight. Animals that achieved a latency of 40 seconds during the baseline trial were included in the study. Experimenters assessing behavior were masked to treatment. Group size was determined using power analysis.
Two graphs show the latency for male or female rats to fall off a rotarod apparatus. Responses are shown at the following time points: baseline (before treatment) and at 1, 2, and 4 hours after treatment with vehicle (10% DMSO and 5% Tween 80 in water, delivered PO) or resatorvid (3, 10, 30, or 100 mg/kg, delivered PO). There were 10 rats per group. Neither males nor females had a significant interaction of time x treatment in a two-way repeated measures ANOVA.


This work was conducted by PsychoGenics Inc. (Paramus, NJ) in collaboration with PSPP, NINDS, NIH under contract # 75N95019D00026 and 75N95024D00038. Prescribing information for clinically used controls can be found at labels.fda.gov. Information for icons representing experimental design details can be found through the NINDS Office of Research Quality https://go.nih.gov/Yw2tHGI.