國家衛生研究院 NHRI:Item 3990099045/10299

NHRI > Institute of Biotechnology and Pharmaceutical Research > Shau-Hua Ueng > Periodical Articles > Item 3990099045/10299

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10299

Title:	1-(2,4-Dibromophenyl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one: A novel opioid receptor agonist with less accompanying gastrointestinal dysfunction than morphine
Authors:	Chao, PK;Ueng, SH;Ou, LC;Yeh, TK;Chang, WT;Chang, HF;Chen, SC;Tao, PL;Law, PY;Loh, HH;Cheng, MF;Chuang, JY;Chen, CT;Shih, C;Yeh, SH
Contributors:	Institute of Biotechnology and Pharmaceutical Research;Center for Neuropsychiatric Research
Abstract:	BACKGROUND: The authors investigated the pharmacology and signaling pathways of the opioid receptors modulated by compound 1, 1-(2,4-dibromophenyl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-4H-indazol-4-one. METHODS: In vitro studies of compound 1 were assessed by using a radioligand-binding assay (n = 3), a cyclic adenosine monophosphate assay (n = 3), a beta-arrestin assay (n = 3), an internalization assay (n = 3), and an immunohistochemistry (n = 8). In vivo studies of compound 1 were characterized using a tail-flick test (n = 5 to 6), tail-clip test (n = 7), von Frey hair test (n = 5), and charcoal meal test (n = 5). RESULTS: Compound 1 elicited robust effects in mu-opioid (mean +/- SD; binding affinity: 15 +/- 2 nM; cyclic adenosine monophosphate assay: 24 +/- 6 nM), delta-opioid (82 +/- 7 nM; 1.9 +/- 0.1 muM), and kappa-opioid (76 +/- 9 nM; 1.4 +/- 0.5 muM) receptor-expressing cells. Compound 1 acts as a full agonist of beta-arrestin-2 recruitment in mu-opioid (1.1 +/- 0.3 muM) and delta-opioid (9.7 +/- 1.9 muM) receptor-expressing cells. Compound 1 caused less gastrointestinal dysfunction (charcoal meal test: morphine: 82 +/- 5%; compound 1: 42 +/- 5%) as well as better antinociception in mechanical pain hypersensitivity (tail-clip test: morphine: 10 +/- 3 s; compound 1: 19 +/- 1 s) and in cancer-induced pain (von Frey hair test: morphine: 0.1 +/- 0.1 g; compound 1: 0.3 +/- 0.1 g) than morphine at equi-antinociceptive doses. CONCLUSIONS: Compound 1 produced antinociception with less gastrointestinal dysfunction than morphine.
Date:	2017-05
Relation:	Anesthesiology. 2017 May;126(5):952-966.
Link to:	http://dx.doi.org/10.1097/aln.0000000000001568
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0003-3022&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000402746000021
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85013127588
Appears in Collections:	[Shau-Hua Ueng] Periodical Articles [Teng-Kuang Yeh] Periodical Articles [Chiung-Tong Chen] Periodical Articles [Chuan Shih(2014-2017)] Periodical Articles [Shiu-Hwa Yeh] Periodical Articles [Pao-Luh Tao] Periodical Articles

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