洛哌丁胺：与μ和δ阿片受体相互作用的证据。

Loperamide: evidence of interaction with mu and delta opioid receptors.

作者信息

Giagnoni G, Casiraghi L, Senini R, Revel L, Parolaro D, Sala M, Gori E

出版信息

Life Sci. 1983;33 Suppl 1:315-8. doi: 10.1016/0024-3205(83)90506-4.

PMID:6319884

Abstract

Loperamide was tested on electrically-evoked contractions using a series of "in vitro" isolated preparations, in comparison with morphine, met-enkephalin, beta-endorphin, ethylketocyclazocine used as representative agonists of mu, delta, epsilon, kappa receptors respectively. The IC50 of loperamide on myenteric plexus longitudinal muscle of guinea pig ileum was found to be 1.90 X 10(-7)M and equal to that of morphine. The IC50 on mouse vas deferens was found to be 13.02 X 10(-7)M. In this tissue, loperamide resulted as active as morphine, but 54 times less active than met-enkephalin (IC50 0.24 X 10(-7)M). On the rat vas deferens where, as expected, beta-endorphin was strongly active (IC50 1.38 X 10(-7)M), morphine exerted a stimulatory action within the range 10(-5)M-10(-4)M and loperamide was only poorly depressive. The Ke value of naloxone, a specific mu receptor antagonist, against loperamide in the guinea pig ileum was 3.83 nM, and in the mouse vas deferens was 82.87 nM indicating that loperamide in the guinea pig ileum acts on mu receptors while in the mouse vas deferens on another opiate receptor.

摘要

洛哌丁胺在一系列“体外”分离制剂上进行了电诱发收缩试验，与吗啡、甲硫氨酸脑啡肽、β-内啡肽、乙基酮环唑辛分别作为μ、δ、ε、κ受体的代表性激动剂进行比较。发现洛哌丁胺对豚鼠回肠肌间神经丛纵肌的IC50为1.90×10⁻⁷M，与吗啡的IC50相等。对小鼠输精管的IC50为13.02×10⁻⁷M。在该组织中，洛哌丁胺的活性与吗啡相当，但比甲硫氨酸脑啡肽（IC50 0.24×10⁻⁷M）低54倍。在大鼠输精管上，正如预期的那样，β-内啡肽具有强烈活性（IC50 1.38×10⁻⁷M），吗啡在10⁻⁵M - 10⁻⁴M范围内发挥刺激作用，而洛哌丁胺仅有微弱的抑制作用。特异性μ受体拮抗剂纳洛酮对豚鼠回肠中洛哌丁胺的Ke值为3.83 nM，对小鼠输精管中洛哌丁胺的Ke值为82.87 nM，表明洛哌丁胺在豚鼠回肠中作用于μ受体，而在小鼠输精管中作用于另一种阿片受体。