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Although 11\u03b2\u2010hydroxysteroid dehydrogenase 1 (11\u03b2\u2010HSD1) is a key enzyme in the intracellular regeneration of glucocorticoids in the CNS, its role in pain perception has not been assessed. Here, we examined the effects of ASP3662, a novel 11\u03b2\u2010HSD1 inhibitor, on neuropathic and dysfunctional pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The enzyme inhibitory activities and pharmacokinetics of ASP3662 were examined, and its antinociceptive effects were evaluated in models of neuropathic pain, fibromyalgia and inflammatory pain in Sprague\u2010Dawley rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>ASP3662 inhibited human, mouse and rat 11\u03b2\u2010HSD1 but not human 11\u03b2\u2010HSD2, <jats:italic>in vitro<\/jats:italic>. ASP3662 had no significant effect on 87 other possible targets (enzymes, transporters and receptors). ASP3662 inhibited <jats:italic>in vitro<\/jats:italic> conversion of glucocorticoid from its inactive to active form in extracts of rat brain and spinal cord. Pharmacokinetic analysis in Sprague\u2010Dawley rats showed that ASP3662 has CNS\u2010penetrability and long\u2010lasting pharmacokinetic properties. Single oral administration of ASP3662 ameliorated mechanical allodynia in spinal nerve ligation (SNL) and streptozotocin\u2010induced diabetic rats and thermal hyperalgesia in chronic constriction nerve injury rats. ASP3662 also restored muscle pressure thresholds in reserpine\u2010induced myalgia rats. Intrathecal administration of ASP3662 was also effective in SNL rats. However, ASP3662 had no analgesic effects in adjuvant\u2010induced arthritis rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>ASP3662 is a potent, selective and CNS\u2010penetrable inhibitor of 11\u03b2\u2010HSD1. The effects of ASP3662 suggest that selective inhibition of 11\u03b2\u2010HSD1 may be an attractive approach for the treatment of neuropathic and dysfunctional pain, as observed in fibromyalgia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14448","type":"journal-article","created":{"date-parts":[[2018,7,14]],"date-time":"2018-07-14T11:54:13Z","timestamp":1531569253000},"page":"3784-3796","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Analgesic effects of <scp>ASP<\/scp>3662, a novel 11\u03b2\u2010hydroxysteroid dehydrogenase 1 inhibitor, in rat models of neuropathic and dysfunctional pain"],"prefix":"10.1111","volume":"175","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0692-4517","authenticated-orcid":false,"given":"Tetsuo","family":"Kiso","sequence":"first","affiliation":[{"name":"Drug Discovery Research Astellas Pharma Inc.  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