典型文献
Novel selective κ agonists SLL-039 and SLL-1206 produce potent antinociception with fewer sedation and aversion
文献摘要：
SLL-039(N-cyclopropylmethyl-7α-4'-(N'-benzoyl)amino-phenyl-6,14-endoethano-tetrahydronorthebaine)and SLL-1206(N-cyclopropylmethyl-7α-3'-(p-methoxybenzyl)amino-phenyl-6,14-endoethano-tetrahydronorthebaine)are two 4,5-epoxymorphinan-based high selective κ receptor agonists that we recently discovered.In the present study we characterized their pharmacological properties in comparison with arylacetamide-based typical κ agonist U50,488H.We showed that both SLL-039 and SLL-1206 produced potent and long-lasting antinociceptive actions in three different rodent models of pain via activation of κopioid receptor.In hot-plate assay,the antinociceptive potency of SLL-039 and SLL-1206 increased about 11-and 17.3-fold compared to U50,488H and morphine,respectively,with ED50 values of 0.4mg/kg.Following repeated administration,SLL-1206,SLL-039,and U50,488H all developed analgesic tolerance tested in hot-plate assay.U50,488H and SLL-039 produced antipruritic effects in a dose-dependent manner,whereas SLL-1206 displayed some antipruritic effects only at very low doses.In addition,SLL-1206 was capable of decreasing morphine-induced physical dependence.More importantly,SLL-039 and SLL-1206 at effective analgesic doses did not cause sedation and conditioned place aversion(CPA),whereas U50,488H did.In comparison with SLL-039,SLL-1206 caused similar antinociceptive responses,but fewer sedation and CPA.In conclusion,our results suggest that SLL-039 and SLL-1206 have potential to be developed as novel analgesic agents,and 4,5-expoxymorphinan scaffold is an attractive structure for the development of selective κ agonists with fewer side effects.
文献关键词：
中图分类号：
作者姓名：
Yuan-yuan Wei;Yan Ma;Song-yu Yao;Ling-hui Kong;Xiao Liu;Jing-rui Chai;Jing Chen;Wei Li;Yu-jun Wang;Li-ming Shao;Jing-gen Liu
作者机构：
School of Basic Medicine and Clinical Pharmacy,China Pharmaceutical University,Nanjing 210009,China;Key Laboratory of Receptor Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China;School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China;Department of Medicinal Chemistry,School of Pharmacy,Fudan University,Shanghai 201203,China
文献出处：
引用格式：
[1]Yuan-yuan Wei;Yan Ma;Song-yu Yao;Ling-hui Kong;Xiao Liu;Jing-rui Chai;Jing Chen;Wei Li;Yu-jun Wang;Li-ming Shao;Jing-gen Liu-.Novel selective κ agonists SLL-039 and SLL-1206 produce potent antinociception with fewer sedation and aversion)[J].中国药理学报（英文版）,2022(06):1372-1382
A类：
antinociception,cyclopropylmethyl,endoethano,tetrahydronorthebaine,methoxybenzyl,epoxymorphinan,arylacetamide,488H,antipruritic,expoxymorphinan
B类：
Novel,selective,agonists,SLL,fewer,sedation,aversion,benzoyl,amino,phenyl,two,high,receptor,that,recently,discovered,In,present,study,characterized,their,pharmacological,properties,comparison,typical,U50,We,showed,both,produced,long,lasting,antinociceptive,actions,three,different,rodent,models,pain,via,activation,opioid,hot,plate,assay,potency,increased,about,compared,morphine,respectively,ED50,values,4mg,Following,repeated,administration,all,developed,analgesic,tolerance,tested,effects,dependent,manner,whereas,displayed,some,only,very,doses,addition,was,capable,decreasing,induced,physical,dependence,More,importantly,effective,did,not,conditioned,place,CPA,caused,similar,responses,but,conclusion,our,results,suggest,have,potential,novel,agents,scaffold,attractive,structure,development,side
AB值：
0.421261
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