Evidence for a Selective Role of the δ-Opioid Agonist [8R-(4bS*,8aα,8aβ,12bβ)]7,10-Dimethyl-1-methoxy-11-(2-methylpropyl)oxycarbonyl 5,6,7,8,12,12b-hexahydro-(9H)-4,8-methanobenzofuro[3,2-e]pyrrolo[2,3-g]isoquinoline Hydrochloride (SB-235863) in Blocking Hyperalgesia Associated with Inflammatory and
Evidence for a Selective Role of the δ-Opioid Agonist [8R-(4bS*,8aα,8aβ,12bβ)]7,10-Dimethyl-1-methoxy-11-(2-methylpropyl)oxycarbonyl 5,6,7,8,12,12b-hexahydro-(9H)-4,8-methanobenzofuro[3,2-e]pyrrolo[2,3-g]isoquinoline Hydrochloride (SB-235863) in Blocking Hyperalgesia Associated with Inflammatory and
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δ-阿片类激动剂选择性作用的证据 [8R-(4bS*,8aα,8aβ,12bβ)]7,10-二甲基-1-甲氧基-11-(2-甲基丙基)氧羰基 5,6,7,8 ,12,12b-六氢-(9H)-4,8-亚甲基苯并呋喃[3,2-e]吡咯并[2,3-g]异喹啉盐酸盐 (SB-235863) 用于阻断与炎症和炎症相关的痛觉过敏
DOI：
10.1124/jpet.103.055590
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发表时间：
2003
影响因子：
3.5
通讯作者：
M. Scheideler
中科院分区：
文献类型：
--
作者：
P. Petrillo;O. Angelici;S. Bingham;Giovanna Ficalora;M. Garnier;P. Zaratin;G. Petrone;O. Pozzi;M. Sbacchi;T. Stean;N. Upton;Guillio M. Dondio;M. Scheideler
通过研究一种选择性、口服活性和中枢渗透的δ-阿片受体激动剂的体内药理活性，探讨了δ-阿片受体在控制伤害感觉中的具体作用。[8R-(4bS*,8aα,8aβ,12bβ)]7,10-二甲基-1-甲氧基-11-（2-甲基丙基）氧羰基5,6,7,8,12,12b-六氢-(9H)-4,8-甲烷苯并呋喃[3,2-e]pyrrolo[2,3-g]异喹啉盐化物（SB-235863）是一种新型pyrrolomorphinan，对δ-阿片受体具有高亲和力（Ki = 4.81±0.39 nM），具有充分的激动剂活性，对μ-和κ-阿片受体的结合选择性分别为189倍和52倍。经口给药SB-236863在大鼠甩尾和热板急性疼痛反应试验中无活性，但能有效逆转由卡拉胶诱导的炎症反应引起的大鼠热痛觉过敏。δ-阿片拮抗剂纳曲多（3mg /kg s.c）可阻断该活性，但选择性μ-和κ-阿片拮抗剂无效。纳曲多（1 μg i.c.v）对10 mg/kg （p.o.）的活性也有阻断作用。SB-235863，表明该化合物激活中枢神经系统的δ-阿片受体位点。SB-235863在经口给药后对部分坐骨神经结扎的Seltzer大鼠模型的慢性痛觉过敏也有效。这些数据表明，δ-阿片受体在调节痛觉性疼痛信号的诱发和持续变化中起选择性作用。给药70 mg/kg （p.o）后，未观察到μ-和κ-阿片受体激活的经典副作用（分别为胃肠道转运减慢和运动不协调）。SB-235863，诱发癫痫活动也没有受到影响。这些结果表明δ-阿片受体在痛觉调节中具有选择性和有限的作用。
The specific involvement of the δ-opioid receptor in the control of nociception was explored by investigating the pharmacological activity in vivo of a selective, orally active, and centrally penetrant δ-opioid agonist. [8R-(4bS*,8aα,8aβ,12bβ)]7,10-dimethyl-1-methoxy-11-(2-methylpropyl)oxycarbonyl 5,6,7,8,12,12b-hexahydro-(9H)-4,8-methanobenzofuro[3,2-e]pyrrolo[2,3-g]isoquinoline hydrochloride (SB-235863) is a new pyrrolomorphinan with high affinity (Ki = 4.81 ± 0.39 nM) for the δ-opioid receptor, full agonist activity, and binding selectivity versus the μ- and κ-opioid receptors of 189-fold and 52-fold, respectively. Perorally administered SB-236863 was inactive in the rat tail-flick and hot-plate tests of acute pain response, but potently reversed thermal hyperalgesia in rats resulting from a carrageenan-induced inflammatory response. This activity could be blocked by the δ-opioid antagonist naltrindole (3 mg/kg s.c.), but selective μ- and κ-opioid antagonists were ineffective. Naltrindole (1 μg i.c.v.) also blocked the activity of 10 mg/kg (p.o.) SB-235863, showing that the compound activates δ-opioid receptor sites in the central nervous system. SB-235863 was additionally effective at reversing chronic hyperalgesia in the Seltzer rat model of partial sciatic nerve ligation after peroral administration. These data show that the δ-opioid receptor plays a selective role in regulating evoked and lasting changes in nociceptive pain signaling. Classical side effects of μ- and κ-opioid receptor activation (slowing of gastrointestinal transit and motor incoordination, respectively) were not observed after administration of 70 mg/kg (p.o.) SB-235863, nor was evoked seizure activity affected. These results suggest a selective and limited role of δ-opioid receptors in the modulation of nociception.
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Delta阿片受体增强μ阿片受体诱导的脊髓镇痛作用。
DOI：
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发表时间：
1998
期刊：
The Journal of pharmacology and experimental therapeutics.
影响因子：
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鞘内注射 β-funaltrexamine 可拮抗小鼠脑室内 β-内啡肽而非吗啡诱导的镇痛作用。
DOI：
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发表时间：
1988
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
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作者：
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发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
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Kappa-和δ-阿片类药物可阻断交感神经依赖性痛觉过敏。
DOI：
10.1523/jneurosci.11-04-00928.1991
发表时间：
1991
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
Taiwo,YO;Levine,JD
通讯作者：
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