Discovery of a Highly Selective and Potent κ Opioid Receptor Agonist from -Cyclopropylmethyl-7α-phenyl-6,14-endoethanotetrahydronorthebaines with Reduced Central Nervous System (CNS) Side Effects Navigated by the Message-Address Concept.

Effective and safe analgesics represent an unmet medical need for the treatment of acute and chronic pain. A series of -cyclopropylmethyl-7α-phenyl-6,14-endoethanotetrahydronorthebaines were designed, synthesized, and assayed, leading to the discovery of a benzylamine derivative (compound , SLL-039) as a highly selective and potent κ opioid agonist (κ, = 0.47 nM, κ/μ = 682, κ/δ = 283), which was confirmed by functional assays and antinociceptive assays .

Pharmacological Characterization of Dezocine, a Potent Analgesic Acting as a κ Partial Agonist and μ Partial Agonist.

Dezocine is becoming dominated in China market for relieving moderate to severe pain. It is believed that Dezocine's clinical efficacy and little chance to provoke adverse events during the therapeutic process are mainly attributed to its partial agonist activity at the μ opioid receptor. In the present work, we comprehensively studied the pharmacological characterization of Dezocine and identified that the analgesic effect of Dezocine was a result of action at both the κ and μ opioid receptors.