Antinociceptive properties of neurosteroids IV: pilot study demonstrating the analgesic effects of alphadolone administered orally to humans.

Fourteen patients scheduled for orthopaedic knee reconstruction surgery were enrolled in a prospective, double-blind, randomized study in which they received alphadolone (25-500 mg, n = 9) or placebo (lactose, n = 5) given orally 1 h after operation. All the subjects received a standardized general anaesthetic and the same type of surgery followed by physiotherapy using a continuous passive movement machine. Morphine was administered intravenously after operation by patient-controlled analgesia. Verbal rating and visual analogue scores assessed pain experiences for 6 h. Orally administered alphadolone up to 500 mg caused no increase in sedation, respiratory depression, nausea or vomiting. The experiences of these side-effects were all rated as none, mild or moderate. Orally administered alphadolone caused statistically significant reductions in morphine use and simultaneous highly significant reductions in pain scores. We conclude that alphadolone is a useful analgesic in humans when given by the oral route.