Selective opiate inhibitor alvinopam
Ileus is a common post-operative complication following abdominal surgery, where peristaltic activity within the ileum is lost, leading to a functional obstruction. It is also a result of treatment with opioid drugs, which are often administered to patients following abdominal surgery, and can lead to post-operative times being extended because of the resultant reduction in bowel motility. If the effects of the opiate drugs on the peripheral tissue in the gastrointestinal tract could be blocked without the pain receptors in the brain being touched, then the chances of ileus developing would be reduced.
A novel opiate under development that could prevent the development of ileus is alvinopam, currently in Phase III trials at Adolor. Alvinopam, previously referred to as ADL 8-2968, is an opioid antagonist with a high affinity for µ-opioid receptors, which also has a low systemic absorption rate as it does not cross the blood/brain barrier, and hence should act in the gut without affecting the analgesic effects of the opiate drugs.
In a study in 79 patients who were undergoing major abdominal surgery (partial colectomy or total abdominal hysterectomy), the subjects were given 1 or 6mg alvinopam or placebo two hours before surgery.1 Further doses were given twice daily after surgery, either until the first bowel movement or until discharge from hospital. All the subjects were given opiate analgesia after the operation. Patients treated with 6mg of alvinopam had a significantly faster recovery of gastrointestinal function than those given placebo 111 to 70 hours. Those treated with the lower dose showed less pronounced effects.
The drug is undergoing Phase III trials, and could well prove a useful addition to the post-operative drug arsenal.