Berzetei-Gurske I P, White A, Polgar W, DeCosta B R, Pasternak G W, Toll L
Department of Neuroscience, SRI International, Menlo Park, CA 94025, USA.
Eur J Pharmacol. 1995 Apr 24;277(2-3):257-63. doi: 10.1016/0014-2999(95)00088-3.
On the basis of its in vivo activity and binding affinity, naloxone benzoylhydrazone has been characterized as a kappa 3-opioid receptor agonist and a mu-opioid receptor antagonist. This paper continues its pharmacological characterization with the help of isolated tissue preparations. Naloxone benzoylhydrazone was found to have partial agonist activity in the guinea pig ileum longitudinal muscle/myenteric plexus preparation. As an antagonist, naloxone benzoylhydrazone is similar to naloxone, with pA2 values of 8.8, 7.8, and 7.8 for mu-, delta-, and kappa 1-opioid receptors, respectively. Its agonist activity in the guinea pig ileum preparation was not influenced by beta-funaltrexamine treatment but was reversed by the selective kappa-opioid receptor antagonist nor-binaltorphimine and by the irreversible kappa 1-opioid receptor blocker UPHIT (1S,2S)-trans-2-isothiocyanato-4,5-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)-cyclohexyl] benzeneacetamide. The presence of kappa 3-opioid receptors could not be demonstrated by [3H]naloxone benzoylhydrazone binding in the guinea pig ileum longitudinal muscle/myenteric plexus preparation. From these studies it is concluded that the partial agonist activity of naloxone benzoylhydrazone in this bioassay is probably due to the activation of the kappa 1-opioid receptors.
基于其体内活性和结合亲和力，纳洛酮苯甲酰腙已被鉴定为κ3-阿片受体激动剂和μ-阿片受体拮抗剂。本文借助离体组织制备继续对其进行药理学特性研究。发现在豚鼠回肠纵肌/肠肌丛制备中，纳洛酮苯甲酰腙具有部分激动剂活性。作为拮抗剂，纳洛酮苯甲酰腙与纳洛酮相似，对μ-、δ-和κ1-阿片受体的pA2值分别为8.8、7.8和7.8。其在豚鼠回肠制备中的激动剂活性不受β-氟纳曲酮处理的影响，但可被选择性κ-阿片受体拮抗剂去甲二丙诺啡和不可逆κ1-阿片受体阻滞剂UPHIT（1S,2S）-反式-2-异硫氰酸基-4,5-二氯-N-甲基-N-[2-（1-吡咯烷基）-环己基]苯乙酰胺逆转。在豚鼠回肠纵肌/肠肌丛制备中，[3H]纳洛酮苯甲酰腙结合未能证明κ3-阿片受体的存在。从这些研究得出结论，在该生物测定中纳洛酮苯甲酰腙的部分激动剂活性可能归因于κ1-阿片受体的激活。
