{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:07:48Z","timestamp":1787238468345,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,3,25]],"date-time":"2013-03-25T00:00:00Z","timestamp":1364169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,4]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n The melastatin\u2010related transient receptor potential\n TRPM<\/jats:styled-content>\n 3 is a calcium\u2010permeable nonselective cation channel that can be activated by the neurosteroid pregnenolone sulphate (\n PregS<\/jats:styled-content>\n ) and heat. T\n RPM<\/jats:styled-content>\n 3\u2010deficient mice show an impaired perception of noxious heat. Hence, drugs inhibiting\n TRPM<\/jats:styled-content>\n 3 possibly get in focus of analgesic therapy.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n Fluorometric methods were used to identify novel\n TRPM<\/jats:styled-content>\n 3\u2010blocking compounds and to characterize their potency and selectivity to block\n TRPM<\/jats:styled-content>\n 3 but not other sensory\n TRP<\/jats:styled-content>\n channels. Biophysical properties of the block were assessed using electrophysiological methods. Single cell calcium measurements confirmed the block of endogenously expressed\n TRPM<\/jats:styled-content>\n 3 channels in rat and mouse dorsal root ganglion (\n DRG<\/jats:styled-content>\n ) neurones.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n By screening a compound library, we identified three natural compounds as potent blockers of\n TRPM<\/jats:styled-content>\n 3. Naringenin and hesperetin belong to the citrus fruit flavanones, and ononetin is a deoxybenzoin. Eriodictyol, a metabolite of naringenin and hesperetin, was still biologically active as a\n TRPM<\/jats:styled-content>\n 3 blocker. The compounds exhibited a marked specificity for recombinant\n TRPM<\/jats:styled-content>\n 3 and blocked\n PregS<\/jats:styled-content>\n \u2010induced [\n C<\/jats:styled-content>\n a\n 2+<\/jats:sup>\n ]\n i<\/jats:sub>\n signals in freshly isolated\n DRG<\/jats:styled-content>\n neurones.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion and Implications<\/jats:title>\n \n The data indicate that citrus fruit flavonoids are potent and selective blockers of\n TRPM<\/jats:styled-content>\n 3. Their potencies ranged from upper nanomolar to lower micromolar concentrations. Since physiological functions of\n TRPM<\/jats:styled-content>\n 3 channels are still poorly defined, the development and validation of potent and selective blockers is expected to contribute to clarifying the role of\n TRPM<\/jats:styled-content>\n 3\n in vivo<\/jats:italic>\n . Considering the involvement of\n TRPM<\/jats:styled-content>\n 3 in nociception,\n TRPM<\/jats:styled-content>\n 3 blockers may represent a novel concept for analgesic treatment.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.12076","type":"journal-article","created":{"date-parts":[[2012,11,28]],"date-time":"2012-11-28T21:10:37Z","timestamp":1354137037000},"page":"1835-1850","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Citrus fruit and fabacea secondary metabolites potently and selectively block\n TRPM<\/scp>\n 3"],"prefix":"10.1111","volume":"168","author":[{"given":"I","family":"Straub","sequence":"first","affiliation":[{"name":"Rudolf\u2010Boehm\u2010Institut f\u00fcr Pharmakologie und Toxikologie Universit\u00e4t Leipzig Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Mohr","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologie und 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