Antinociceptive profile of biphalin, a dimeric enkephalin analog.
Antinociceptive profile of biphalin, a dimeric enkephalin analog.
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发表时间：
1993-06
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通讯作者：
Peter J. Horan;A. Mattia;E. Bilsky;S. J. Weber;T. Davis;H. Yamamura;E. Malatyńska;S. Appleyard;J. Slaninová;A. Misicka
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作者：
Peter J. Horan;A. Mattia;E. Bilsky;S. J. Weber;T. Davis;H. Yamamura;E. Malatyńska;S. Appleyard;J. Slaninová;A. Misicka
用抗伤害性、胃肠和身体依赖模型对二聚脑啡肽双酚(Try-D-Ala-Gly-Phe-NH)2在小鼠体内进行了评价，并与吗啡(MU参比激动剂)和依托啡(超强阿片激动剂)进行了比较。脑室注射的双酚A在诱导抗伤害性感觉方面的效力是依托吗啡或吗啡的6.7和257倍。在甩尾试验中，即使给药剂量比有效静脉注射高出3个数量级，毕非林在甩尾试验中也只产生60%的最大抗伤害效应；当静脉注射吗啡时，在本实验中吗啡是等量的。或IT。腹腔注射吗啡和双酚A后，吗啡和双酚的作用相同。行政管理。尽管它在ipp后有抗伤害作用。行政管理。尽管它在ipp后有抗伤害作用。给药后，只有一小部分[125I]联苯双酚通过脑(20min时为0.051+/-0.011%)。在I.C.V.之后。给药后，受体选择性剂量的β-Funaltrexamine(Mu拮抗剂)、Naloxonazine(Mu 1拮抗剂)、ICI174,864(Delta拮抗剂)和[D-Ala2，Cys4]Deltorphin(Delta2拮抗剂)可拮抗Biphalin的抗伤害作用，但[D-Ala2，Leu5，Cys6]脑啡肽(Delta 1拮抗剂)或Nor-binaltorphimine(Kappa拮抗剂)不能拮抗Biphalin的拮抗作用，而依托吗啡的拮抗作用仅被β-Funalaltrexine和Naloxonazine所拮抗。脑室注射的双酚A抑制胃肠推进的剂量是静脉注射的8倍。抗伤害性；I.C.V.吗啡表现出类似的抗伤害感受性和胃肠推进A50。腹膜内注射比法林，但不是ip。吗啡，即使有身体依赖，也很少，但当静脉注射相同剂量的伤害性感受性药物时，比法林和吗啡都会产生显著的身体依赖。
The dimeric enkephalin biphalin (Try-D-Ala-Gly-Phe-NH)2 was evaluated in mice using antinociceptive, gastrointestinal and physical dependence paradigms and compared with that of morphine (reference mu agonist) and etorphine (ultrapotent opioid agonist). Intracerebroventricular biphalin was 6.7- and 257-fold more potent than etorphine or morphine in eliciting antinociception. When administered i.t., biphalin produced only a 60% maximal antinociceptive effect in the tail-flick test even when given at doses up to 3 orders of magnitude higher than those effective i.c.v.; morphine was equipotent in this assay when given i.c.v. or i.t. Both morphine and biphalin were equipotent after i.p. administration. In spite of its antinociceptive effectiveness after i.p. administration. In spite of its antinociceptive effectiveness after i.p. administration, only a small fraction of [125I]biphalin was shown to penetrate to the brain (0.051 +/- 0.011%, at 20 min). After i.c.v. administration, biphalin antinociception was antagonized by receptor selective doses of beta-funaltrexamine (mu antagonist), naloxonazine (mu 1 antagonist), ICI 174,864 (delta antagonist) and [D-Ala2,Cys4]deltorphin (delta 2 antagonist), but not by [D-Ala2,Leu5,Cys6]enkephalin (delta 1 antagonist) or nor-binaltorphimine (kappa antagonist), whereas etorphine antinociception was significantly antagonized only by beta-funaltrexamine and naloxonazine. Intracerebroventricular biphalin inhibited gastrointestinal propulsion at doses 8-fold higher than those producing i.c.v. antinociception; i.c.v. morphine showed a similar antinociceptive and gastrointestinal propulsion A50. Intraperitoneal biphalin, but not i.p. morphine, showed little, if any, physical dependence, but both biphalin and morphine produced significant physical dependence when equiantinociceptive doses were infused i.c.v.(ABSTRACT TRUNCATED AT 250 WORDS)