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Development of PAC-14028, a novel transient receptor potential vanilloid type 1 (TRPV1) channel antagonist as a new drug for refractory skin diseases Lim KM; Park YHArch Pharm Res 2012[Mar]; 35 (3): 393-6The transient receptor potential vanilloid 1 (TRPV1) is a member of nonselective cation channels and has been implicated in the progression of neurogenic inflammation and nociception. Through the synthesis of over 2,000 new compounds, a novel non-vanilloid TRPV1 antagonist PAC-14028 was discovered. As well as ideal physicochemical and pharmacokinetic properties, PAC-14028 showed meaningful efficacies against diverse disease models that include visceral pain, inflammatory bowel disease, and inflammatory pain. Of note, PAC-14028 effectively attenuates atopic dermatitis and pruritus without significant adverse effects, which is a substantial benefit over conventional pharmacotherapy. This report introduces the potential of a novel TRPV1 antagonist PAC-14028 as a new drug for atopic dermatitis and pruritus.|Acrylamides/adverse effects/*therapeutic use[MESH]|Animals[MESH]|Anti-Inflammatory Agents/adverse effects/*therapeutic use[MESH]|Antipruritics/adverse effects/*therapeutic use[MESH]|Dermatitis, Atopic/*drug therapy/metabolism[MESH]|Disease Models, Animal[MESH]|Drugs, Investigational/adverse effects/*therapeutic use[MESH]|Humans[MESH]|Pruritus/*drug therapy/metabolism[MESH]|Pyridines/adverse effects/*therapeutic use[MESH]|TRPV Cation Channels/*antagonists & inhibitors/metabolism[MESH] |
