國家衛生研究院 NHRI:Item 3990099045/4944

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/4944

Title:	Biphasic suppression of appetite by cannabinoid CB1 receptor antagonists with distinct functional activities
Authors:	Lin, Y;Shia, KS;Hsiao, WC;Hsieh, WP;Yeh, TK;Tseng, SL;Hsu, CY;Chao, YS;Hung, MS
Contributors:	Division of Biotechnology and Pharmaceutical Research
Abstract:	A novel alkynylthiophene series of cannabinoid CB1 receptor antagonists has been described to exhibit distinct intrinsic activities with minimal substructure modifications. The three representatives, BPR0432, BPR0568 and BPR0569, functioning as a neutral antagonist, an inverse agonist and a partial agonist, respectively, in GTP binding assay, were further characterized for their downstream signaling activities in relation to in vivo efficacy in appetite suppression to diets of different macronutrients. Interestingly, these three derivatives all behaved as inverse agonists with the potency of BPR0432>BPR0568>BPR0569 in cAMP assay. After administered to non-deprived rats, the potency in appetite suppression was positively related to their strength in intrinsic activity in the first hour of intake. The preferential suppression to high fat and high carbohydrate diets was revealed after 6h and only appeared in the treatment of BPR0568, presumably due to its metabolic stability in addition to its intrinsic activity. These results indicated the suppression of appetite was controlled in a biphasic manner, and these three structurally close but functionally distinct compounds are invaluable tools in elucidating the mechanism of neuronal response to appetite and palatability.
Date:	2010-10
Relation:	Pharmacological Research. 2010 Oct;62(4):337-343.
Link to:	http://dx.doi.org/10.1016/j.phrs.2010.06.001
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1043-6618&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000281368600007
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77955278071
Appears in Collections:	[Ming-Shiu Hung] Periodical Articles [Teng-Kuang Yeh] Periodical Articles [Kak-Shan Shia] Periodical Articles [Yu-Sheng Chao(2002-2013)] Periodical Articles

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