Analgesic activity and opioid receptor selectivity of stereoisomers of ohmefentanyl isothiocyanate

doi:10.1016/S0014-2999(01)01172-4

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	Analgesic activity and opioid receptor selectivity of stereoisomers of ohmefentanyl isothiocyanate
	Chen, BY; Jin, WQ; Chen, XJ; Zhu, YC; Chi, ZQ
刊名	EUROPEAN JOURNAL OF PHARMACOLOGY
	2001-07-27
卷号	424 期号:3 页码:195-198
关键词	ohmefentanyl isothiocyanate stereoisomer opioid receptor analgesia bioassay receptor binding
ISSN号	0014-2999
DOI	10.1016/S0014-2999(01)01172-4
文献子类	Article
英文摘要	Ohmefentanyl is a very potent and highly selective agonist for mu -opioid receptors. We now study analgesia, in vitro activity and opioid receptor affinity of the stereoisomers of ohmefentanyl isothiocyanate. We found that some isomers of ohmefentanyl. isothiocyanate had a potent analgesic effect and that all isomers except (3R,4S,2'S)-ohmefentanyl isothiocyanate had a more potent inhibitory action on the electrically evoked contractions of mouse vas deferens than of guinea pig ileum. The inhibitory actions could be antagonized by naloxone. However, compared with the activity of the corresponding stereoisomers of ohmefentanyl, these ohmefentanyl isothiocyanates had significantly reduced analgesia and in vitro activity. They also inhibited the binding of [H-3]DPDPE ([D-Pen(2),D-Pen(5)]enkephalin) and [H-3]DAGO ([D-Ala(2),Mephe(4),Gly-ol(5)]enkephalin) to opioid receptors in mouse brain membranes. The inhibitory effect of stereoisomers of ohmefentanyl isothiocyanate at mu -opioid receptors was markedly lower than that of their parent compounds. The affinity of stereoisomers of ohmefentanyl isothiocyanate, for delta -opioid receptors was, however, greater than or equal to that of their corresponding stereoisomers of ohmefentanyl. The results showed that the introduction of an isothiocyanato group into the phenyl ring in position-1 of ohmefentanyl reduced bioactivity and affinity to mu -opioid receptors but that the selectivity of these compounds for delta -opioid receptors was enhanced. Isomer (3R,4S,2'R)-ohmefentanyl isothiocyanate showed highest selectivity for delta -opioid receptors (K-i(mu)/K-i(delta) = 13.6) and potent analgesic activity (ED50 = 0.25 mg/kg). (C) 2001 Elsevier Science BY. All rights reserved.
WOS关键词	DIRECTED ACYLATING AGENT ; MEDIATED PHENOMENA ; IRREVERSIBLE LIGANDS ; OPIATE RECEPTORS ; DELTA-OPIATE ; MU-OPIATE ; PROBES
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000170467900005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/274468]
专题	药理学第一研究室
通讯作者	Jin, WQ
作者单位	Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Dept Pharmacol 2, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Chen, BY,Jin, WQ,Chen, XJ,et al. Analgesic activity and opioid receptor selectivity of stereoisomers of ohmefentanyl isothiocyanate[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2001,424(3):195-198.
APA	Chen, BY,Jin, WQ,Chen, XJ,Zhu, YC,&Chi, ZQ.(2001).Analgesic activity and opioid receptor selectivity of stereoisomers of ohmefentanyl isothiocyanate.EUROPEAN JOURNAL OF PHARMACOLOGY,424(3),195-198.
MLA	Chen, BY,et al."Analgesic activity and opioid receptor selectivity of stereoisomers of ohmefentanyl isothiocyanate".EUROPEAN JOURNAL OF PHARMACOLOGY 424.3(2001):195-198.