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Outstanding examples include neuroinhibitory medications like antiseizure drugs, which are used against epilepsy and neuropathic pain but cause systemic side effects. There is a need of drugs that inhibit nerve signals locally and on\u2010demand without affecting other regions of the body. Photopharmacology aims to address this problem with light\u2010activated drugs and localized illumination in the target organ. Here, we have developed photoswitchable derivatives of the widely prescribed antiseizure drug carbamazepine. For that purpose, we expanded our method of <jats:italic>ortho<\/jats:italic> azologization of tricyclic drugs to <jats:italic>meta<\/jats:italic>\/<jats:italic>para<\/jats:italic> and to N\u2010bridged diazocine. Our results validate the concept of <jats:italic>ortho<\/jats:italic> cryptoazologs (uniquely exemplified by Carbazopine\u2010<jats:bold>1<\/jats:bold>) and bring to light Carbadiazocine (<jats:bold>8<\/jats:bold>), which can be photoswitched between 400\u2013590\u2005nm light (using violet LEDs and halogen lamps) and shows good drug\u2010likeness and predicted safety. Both compounds display photoswitchable activity <jats:italic>in vitro<\/jats:italic> and in translucent zebrafish larvae. Carbadiazocine (<jats:bold>8<\/jats:bold>) also offers <jats:italic>in vivo<\/jats:italic> analgesic efficacy (mechanical and thermal stimuli) in a rat model of neuropathic pain and a simple and compelling treatment demonstration with non\u2010invasive illumination.<\/jats:p>","DOI":"10.1002\/anie.202403636","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T07:26:52Z","timestamp":1718695612000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Photoswitchable Carbamazepine Analogs for Non\u2010Invasive Neuroinhibition <i>In Vivo<\/i>"],"prefix":"10.1002","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9942-7220","authenticated-orcid":false,"given":"Luisa","family":"Camerin","sequence":"first","affiliation":[{"name":"Institute for Bioengineering of Catalonia (IBEC) The Barcelona Institute for Science and Technology  Barcelona 08028 Spain"},{"name":"Networking Biomedical Center in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN) ISCIII  Madrid 28029 Spain"},{"name":"Doctorate program in organic chemistry University of Barcelona  Barcelona 08028 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galyna","family":"Maleeva","sequence":"additional","affiliation":[{"name":"Institute for Bioengineering of Catalonia (IBEC) The Barcelona Institute for Science and Technology  Barcelona 08028 Spain"},{"name":"Networking Biomedical Center in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN) ISCIII  Madrid 28029 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre M. 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