title: TRPV1 activation is not an all-or-none event: TRPV1 partial agonism/antagonism and its regulatory modulation.
abstract: TRPV1 has emerged as a promising therapeutic target for pain as well as a broad range of other conditions such as asthma or urge incontinence. The identification of resiniferatoxin as an ultrapotent ligand partially able to dissect the acute activation of TRPV1 from subsequent desensitization and the subsequent intense efforts in medicinal chemistry have revealed that TRPV1 affords a dramatic landscape of opportunities for pharmacological manipulation. While agonism and antagonism have represented the primary directions for drug development, the pharmacological complexity of TRPV1 affords additional opportunities. Partial agonism/partial antagonism, its modulation by signaling pathways, variable desensitization, and slow kinetics of action can all be exploited through drug design.
authors.affiliation: Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4255, USA. blumberp@dc37a.nci.nih.gov
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
authors.forename: Larry V
authors.initials: LV
authors.lastname: Pearce
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D004224:Diterpenes / Q000494:pharmacology; D015195:Drug Design; D054333:Drug Partial Agonism; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004224:Diterpenes; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C024353:resiniferatoxin; D002211:Capsaicin