Selective sigma-1 receptor antagonists for the treatment of pain.

The sigma-1 receptor (σ1R) is located in areas of the CNS key for pain control and belongs to a unique target class with chaperoning functions over different molecular targets involved in transmission and amplification of nociceptive messages. Preclinical evidence supports a role for σ1R antagonists in the treatment of pain states where hypersensitivity develops as hyperalgesia and allodynia, two common symptoms encountered in neuropathic and other chronic pain conditions. Additionally, σ1R antagonists increase opioid analgesia without increasing opioid-related unwanted effects, which point to their potential use as opioid adjuvant therapy. This review summarizes the structure and function of the σ1R as well as the medicinal chemistry and pharmacological studies directed to the identification of σ1R antagonists for the treatment of pain.