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Novel developments with selective, non-peptidic kappa-opioid receptor agonists
1Department of CNS Research, Preclinical Pharmaceutical Research, Merck KGaA, 64271 Darmstadt, Germany.
Expert Opinion on Investigational Drugs
|July 2, 2005
Summary
Pharmaceutical companies show waning interest in developing kappa opioid agonists due to side effects. While some drugs face discontinuation, others show promise for specific conditions like cancer pain and rheumatic disorders.
Area of Science:
- Pharmacology
- Neuroscience
- Drug Development
Background:
- Pharmaceutical interest in centrally-acting kappa opioid agonists has declined.
- Clinical trials for several compounds have been discontinued, often with unclear reasons.
Purpose of the Study:
- To review the current status and challenges in the development of kappa opioid agonists.
- To highlight specific compounds, their therapeutic targets, and clinical trial outcomes.
Main Methods:
- Review of clinical trial data and published literature on kappa opioid agonists.
- Analysis of reasons for trial discontinuation and side effect profiles.
Main Results:
- Spiradoline and enadoline abandoned as analgesics due to dysphoria.
- Niravoline development halted for hyponatraemic disorders.
- Enadoline, apadoline, and TRK 820 are in ongoing trials for specific indications.
- Peripherally-acting asimadoline and atypical fedotozine show good tolerability but mixed efficacy results.
Conclusions:
- Development of kappa opioid agonists faces challenges, primarily due to central side effects.
- Peripherally-selective or atypical compounds may offer better tolerability.
- Further research and clinical trials are needed to ascertain the therapeutic potential of remaining candidates.