Related Experiment Video
Updated: Jun 25, 2025

Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery
Published on: April 14, 2016
Systematic Structure-Activity Relationship Study of Nalfurafine Analogues toward Development of Potentially
Celsey M St Onge1, Piyusha P Pagare1, Yi Zheng1
1Department of Medicinal Chemistry, Virginia Commonwealth University, 800 E. Leigh Street, Richmond, Virginia 23219, United States.
Abstract:
Despite the availability of numerous pain medications, the current array of Food and Drug Administration-approved options falls short in adequately addressing pain states for numerous patients and consequently worsens the opioid crisis. Thus, it is imperative for basic research to develop novel and nonaddictive pain medications. Toward addressing this clinical goal, nalfurafine (NLF) was chosen as a lead and its structure-activity relationship (SAR) systematically studied through design, syntheses, and in vivo characterization of 24 analogues. Two analogues, 21 and 23, showed longer durations of action than NLF in a warm-water tail immersion assay, produced in vivo effects primarily mediated by KOR and DOR, penetrated the blood-brain barrier, and did not function as reinforcers. Additionally, 21 produced fewer sedative effects than NLF. Taken together, these results aid the understanding of NLF SAR and provide insights for future endeavors in developing novel nonaddictive therapeutics to treat pain.
Related Concept Videos
Opioid Analgesics: Synthetic and Semisynthetic Opioids
Analgesia and Pain Management
Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
Opioid Analgesics: Morphine and Other Natural Cogeners
Local Anesthetics: Chemistry and Structure-Activity Relationship
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...

