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• W2598403906 startingPage "386" @default.
• W2598403906 abstract "The purpose of this study was to evaluate the skin permeation of tricyclic antidepressants (TCAs) with propamine moiety to select candidates for the development of topical analgesics to treat cutaneous pain. We sought to establish the structure-permeation relationship (SPR) of topical TCAs. The lipophilicity, melting point, and aqueous solubility were determined to develop the physicochemical characterization. The TCA permeation into pig and nude mouse skins was estimated using Franz diffusion cell. TCAs and lidocaine were comparatively examined for cutaneous analgesia by pinprick assay. Cutaneous tolerance to TCAs was assessed using nude mouse skin. The skin deposition increased following the increase of lipophilicity after excluding the effect of solubility, with clomipramine exhibiting the highest skin retention. A contrary result was observed for TCA penetration into the receptor. Of the permeants tested, clomipramine demonstrated the best skin-targeting ability. Nortriptyline and clomipramine demonstrated selective uptake into the hair follicles, exhibiting a 2.5-fold higher follicular accumulation than desipramine. Replacement of nitrogen with carbon in the seven-member ring increased skin absorption. The tertiary amine TCAs demonstrated higher absorption than the secondary amine TCAs. The position of the double bond also affected skin transport. Topical clomipramine had a longer duration of analgesic action than lidocaine (240min versus 60min). Exploring the SPR revealed that clomipramine could be an analgesic candidate drug for future development." @default.
• W2598403906 created "2017-04-07" @default.
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• W2598403906 date "2017-05-01" @default.
• W2598403906 modified "2023-09-23" @default.
• W2598403906 title "Exploring the structure-permeation relationship of topical tricyclic antidepressants used for skin analgesia" @default.
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• W2598403906 doi "https://doi.org/10.1016/j.ijpharm.2017.03.048" @default.
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