TABLE 4

Opioid-induced clinical signs

The degrees of the clinical signs are scored as 0 = none, 1 = mild, 2 = moderate and 3 = severe. Values shown in the degree columns are the mean degree score for each symptom. Total score = total sum of N × degree. Rats that displayed a score of 1 or higher on 3 or more signs were considered to display opioid-induced behavior.

Clinical Signs (1 h postdose)No P-gp ModulatorElacridar 1.0 mg/kgTariquidar 1.0 mg/kgElacridar 0.5 mg/kg+ Tariquidar 0.5 mg/kg
N/nDegreeN/nDegreeN/nDegreeN/nDegree
Central nervous system
 Lethargy0/1206/1224/1229/123
 Whole-body tetany0/1200/1200/1209/122
 Straub tail0/1200/1200/1202/123
 Piloerection0/1204/1213/1217/122
 Pulmonary
 Shallow breathing0/1205/1222/1219/123
Eyes
 Eye protrusion0/1200/1200/1205/122
 Total score02613102
  • N/n, number of rats displaying these clinical signs/number of rats per group (n = 12).