Selective sigma-1 receptor antagonists for the treatment of pain

The sigma-1 receptor (sigma R-1) 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 sigma R-1 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, sigma R-1 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 sigma R-1 as well as the medicinal chemistry and pharmacological studies directed to the identification of sigma R-1 antagonists for the treatment of pain.