LY-255582

Names

[ CAS No. ]:
119193-09-8

[ Name ]:
LY-255582

[Synonym ]:
(+)-1-[(3S)-3-Hydroxy-3-cyclohexylpropyl]-(3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine
(+)-1-(3(S)-3-hydroxy-3-cyclohexylpropyl)-3(R),4(R)-dimethyl-4-(3-hydroxyphenyl)piperidine

Biological Activity

[Description]:

LY255582 is a pan-opioid antagonist and has high affinity for mu, delta, and kappa receptors (Ki: 0.4 nM, 5.2, 2.0 nM respectively). LY255582 can decrease food intake and body weight. LY255582 can be used for the research of obesity[1][2][3][4].

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> Opioid Receptor

Research Areas >> Metabolic Disease

Signaling Pathways >> Neuronal Signaling >> Opioid Receptor

[Target]

μ Opioid Receptor/MOR:0.4 nM (Ki)

δ Opioid Receptor/DOR:5.2 nM (Ki)

κ Opioid Receptor/KOR:2.0 nM (Ki)

[In Vitro]

LY255582 (40 μM, 24-72 h) 抑制 Huh7 和 MHCC-97H 细胞活力[5]。

[In Vivo]

LY255582 (100 μg，i.c.v.) 减少大鼠的食物摄入量[1]。 LY255582 (15 mg/kg，皮下注射，每日一次) 减少喂食的肥胖 Zucker 大鼠的食物摄入量和体重增加[4]。 Animal Model: STZ-induced diabetic mice[1] Dosage: 100, 10 and 1 μg Administration: i.c.v. Result: Decreased food at 100, 10 and 1 μg by 76, 62 and 29%.

[References]

[1]. Levine AS, et al. Central administration of the opioid antagonist, LY255582, decreases short- and long-term food intake in rats. Brain Res. 1991 Dec 6;566(1-2):193-7.

[2]. Need AB, et al. In vivo rat brain opioid receptor binding of LY255582 assessed with a novel method using LC/MS/MS and the administration of three tracers simultaneously. Life Sci. 2007 Oct 13;81(17-18):1389-96.

[3]. S.L. Gackenheimer, et al. Localization of opioid receptor antagonist [3H]-LY255582 binding sites in mouse brain: Comparison with the distribution of mu, delta and kappa binding sites. Neuropeptides. 2005. 39 (6), 559-567.

[4]. Shaw WN, et al. Long-term treatment of obese Zucker rats with LY255582 and other appetite suppressants. Pharmacol Biochem Behav. 1993 Nov;46(3):653-9.

[5]. Chen DT, et al. The mu-opioid receptor is a molecular marker for poor prognosis in hepatocellular carcinoma and represents a potential therapeutic target. Br J Anaesth. 2019 Jun;122(6):e157-e167.

Chemical & Physical Properties

[ Molecular Formula ]:
C₂₂H₃₅NO₂

[ Molecular Weight ]:
345.51900

[ Exact Mass ]:
345.26700

[ PSA ]:
43.70000

[ LogP ]:
4.26090

Safety Information

[ RIDADR ]:
NONH for all modes of transport

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Activation of mesolimbic dopamine neurons during novel and daily limited access to palatable food is blocked by the opioid antagonist LY255582.

Am. J. Physiol. Regul. Integr. Comp. Physiol. 295(2) , R463-71, (2008)

An analog of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine series (LY255582) exhibits high in vitro binding affinity and antagonist potency for the mu-, delta-, and kappa-opioid receptors. In v...