Method and composition for treating irritable bowel syndrome using low doses of opioid receptor antagonists

Abstract

This invention relates to a method for treating a subject with irritable bowel syndrome (“IBS”) which comprises long-term administration of an opioid receptor antagonist at an appropriately low dose which will selectively antagonize excitatory opioid receptor functions, but not inhibitory opioid receptor functions, in myenteric neurons in the intestinal tract as well as in neurons of the central nervous system (“CNS”). The administration of the opioid receptor antagonist at a low dose enhances the potency of the inhibitory effects of endogenous opioid peptides present in the intestinal tract and the CNS, thereby reducing abdominal pain and stool frequency resulting from abnormally supersensitized excitatory opioid receptor functions. The invention also relates to a composition for treating a subject with IBS, which comprises an effective dose of an opioid receptor antagonist, and a pharmaceutically acceptable carrier.

Description

FIELD OF THE INVENTION [0001] This invention relates to a method for treating a subject with irritable bowel syndrome (“IBS”) which comprises administering a low dose of an opioid receptor antagonist to the subject. Specifically, this invention relates to a method for treating a subject with IBS by the long-term administration of an opioid receptor antagonist at an appropriately low dose which will selectively antagonize excitatory opioid receptor functions, but not inhibitory opioid receptor functions, in myenteric neurons in the intestinal tract as well as in neurons of the central nervous system (“CNS”). The administration of the opioid receptor antagonist at a low dose enhances the potency of the inhibitory effects of endogenous opioid peptides present in the intestinal tract and the CNS, thereby reducing abdominal pain and stool frequency resulting from abnormally supersensitized excitatory opioid receptor functions. The invention also relates to a composition for treating a su...

AI Technical Summary

Problems solved by technology

Furthermore, there are also increased or unusual areas of visceral pain.

The end organ therapy treatments for IBS have proved ineffective or contain inherent drawbacks that limit their usefulness.

For example, while the gut accelerants are useful to accelerate gut transit, they also exacerbate abdominal pain and bloating.

Likewise, while antidiarrheals, such as loperamide, are often effective in treating diarrhea-predominant IBS, they are ineffective in treating the additional symptoms associated with IBS, such as abdominal pain.

As a consequence, end organ therapy often is limited to patients with mild or moderate symptoms.

In addition, some of the most effective compounds in these classes are not available for use in the United States, since they have not been approved by the Federal Food and Drug Administration (Committee, 1997).

Finally, dietary alterations are of limited utility for a small segment of IBS patients.

However, because of their psychotropic properties, administration of these drugs requires long-term care, and are usually only given to patients with severe or refractory symptoms, impaired daily function, and associated depression or anxiety attacks.

Furthermore, the newer antidepressants, in particular the specific serotonin reuptake inhibitors, such as fluoxetine, serraline, and paroxetine, have not been shown to be more effective than the tricyclic antidepressants, although some anecdotal evidence suggests these compounds may have fewer side effects (Committee, 1997).

While the patients reported decreased transit time and increased stool frequency, nalmefene glucuronide did not reduce abdominal pain or bloating, and stool consistency was not improved.

However, there is no teaching or suggestion in U.S. Pat. No. 5,512,578 that administration of a selective excitatory opioid receptor antagonist would be useful in treating symptoms of IBS.

In particular, there is no teaching or suggestion that administration of a selective excitatory opioid receptor antagonist would be useful in treating symptoms of IBS that are unrelated to the nociceptive pathways, such as stool frequency or consistency.

However, U.S. Pat. No. 5,472,943 does not disclose that a selective excitatory opioid receptor antagonist can be used in the absence of a bimodally-acting opioid agonist.

In particular, there is no teaching or suggestion that administration of a selective excitatory opioid receptor antagonist would be useful in treating other symptoms of IBS, such as stool frequency or consistency.

However, U.S. Pat. No. 5,585,348 does not disclose that the selective opioid receptor antagonist may be administered in the absence of nerve growth factor, and does not teach or suggest that the administration of a selective excitatory opioid receptor antagonist alone would be useful in treating IBS.