{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:12:10Z","timestamp":1790327530161,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Crisugabalin (HSK16149) is a next\u2010generation \u03b12\u03b4 ligand developed to preserve the mechanistic rationale of gabapentinoids while refining target engagement and exposure\u2010related tolerability constraints. We performed a translational review of molecular\/structural studies, in vivo pharmacology and behavioural safety assessments, phase I clinical pharmacology and randomized clinical trials in diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN), with searches across major bibliographic databases and trial registries updated through June 2026. Evidence was synthesized qualitatively along a molecular\u2010to\u2010clinical sequence. Structural and kinetic studies indicate stable engagement of the \u03b12\u03b41 binding site, with slower dissociation from \u03b12\u03b41 than from \u03b12\u03b42. In rodent models, crisugabalin demonstrated antinociceptive efficacy with a wider separation between antinociceptive and motor\u2010impairing doses relative to pregabalin and no clear abuse liability signals across standard paradigms. Human phase I data show rapid absorption (T\n                    <jats:sub>max<\/jats:sub>\n                    \u2009~\u20091.5\u20131.7\u2009h), dose\u2010proportional exposure, slight accumulation and predominant renal elimination. A high\u2010fat meal delayed absorption without materially changing overall exposure, whereas renal impairment produced graded exposure increases supporting consideration of dose adjustment as renal function declines. Clinically, a seamless adaptive phase II\/III trial in DPNP and a confirmatory phase III trial in PHN demonstrated significant reductions in pain intensity at 40\u201380\u2009mg\/day; dizziness was the most frequent dose\u2010related adverse event. Current evidence supports crisugabalin as a class\u2010refinement strategy with consistent short\u2010term efficacy in DPNP and PHN and predictable clinical pharmacology. Generalizability beyond Chinese populations, longer\u2010term outcomes and comparative effectiveness relative to established therapies remain key gaps.\n                  <\/jats:p>","DOI":"10.1002\/bcp.70821","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:52:20Z","timestamp":1790326340000},"source":"Crossref","is-referenced-by-count":0,"title":["Translational development of crisugabalin for neuropathic pain"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4518-2090","authenticated-orcid":false,"given":"Rafael Batista","family":"Jo\u00e3o","sequence":"first","affiliation":[{"name":"Neurology and Neurophysiology Department Goi\u00e2nia Neurological Institute  Goi\u00e2nia Goi\u00e1s Brazil"},{"name":"Neuroscience Center Clinics Hospital, Federal University of Goi\u00e1s  Goi\u00e2nia Goi\u00e1s Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jilly Octoria","family":"Tagore Chan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine University of Indonesia  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00edsa Mendes","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Federal University of Par\u00e1  Bel\u00e9m Par\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Batista","family":"Jo\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Jos\u00e9 Alencar City Hospital  S\u00e3o Bernardo do Campo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel Mattos","family":"Filgueiras","sequence":"additional","affiliation":[{"name":"Department of Neurology Dr. Jos\u00e9 de Carvalho Florence City Hospital  S\u00e3o Jos\u00e9 dos Campos S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo C\u00e9sar","family":"Ragazzo","sequence":"additional","affiliation":[{"name":"Neurology and Neurophysiology Department Goi\u00e2nia Neurological Institute  Goi\u00e2nia Goi\u00e1s 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