Behavioral pharmacology of the mixed-action delta-selective opioid receptor agonist BBI-11008: studies on acute, inflammatory and neuropathic pain, respiration, and drug self-administration.
Behavioral pharmacology of the mixed-action delta-selective opioid receptor agonist BBI-11008: studies on acute, inflammatory and neuropathic pain, respiration, and drug self-administration.
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DOI：
10.1007/s00213-019-05449-z
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发表时间：
2020-04
影响因子：
3.4
通讯作者：
Bilsky EJ
中科院分区：
文献类型：
--
作者：
Stevenson GW;Giuvelis D;Cormier J;Cone K;Atherton P;Krivitsky R;Warner E;St Laurent B;Dutra J;Bidlack JM;Szabò L;Polt R;Bilsky EJ
本研究描述了一种新型的混合作用三角洲选择性阿片受体激动剂BBI-11008的行为药理学。这种糖肽候选药物在评估抗感觉性（急性、炎症和神经性疼痛样疾病）和副作用终点（呼吸抑制和药物自我给药）的试验中进行了测试。BBI-11008对δ阿片受体的亲和力比mu受体高78倍，与kappa阿片受体没有结合。BBI-11008 （3.2 - 100; 10 - 32 mg/kg，静脉注射）和吗啡（1 - 10;1 - 3.2 mg/kg，静脉注射）在急性热伤害性和完全性弗氏佐剂（CFA）诱导的炎症性疼痛试验中产生抗痛觉和抗异动作用，BBI-11008在这两项试验中的效力都低于吗啡。BBI-11008 （1 - 18mg /kg，静脉注射）与加巴喷丁（10 - 56mg /kg，静脉注射）在神经性疼痛脊神经结扎（SNL）模型中的疗效相似。在呼吸试验中，随着%CO2暴露的增加，BBI-11008在分钟体积（MV）中产生最初的增加（32 mg/kg, s.c），然后下降（56 mg/kg, s.c），而吗啡（3.2 - 32 mg/kg, s.c）产生剂量依赖性的MV下降。在药物自我给药过程中，BBI-11008在任何测试剂量下都没有保持自我给药。这些结果表明，糖肽候选药物在一系列疼痛样疾病中具有广谱抗痛觉性和抗异动性活性。相对于吗啡或芬太尼，BBI-11008在呼吸和药物自我给药试验中的特征表明，BBI-11008可能没有那么明显的有害副作用。继续评估这种化合物是有必要的。
The present study characterized the behavioral pharmacology of a novel, mixed-action delta-selective (78:1) opioid receptor agonist, BBI-11008. This glycopeptide drug candidate was tested in assays assessing antinociception (acute, inflammatory, and neuropathic pain-like conditions), and side-effect endpoints (respiratory depression and drug self-administration). BBI-11008 had a 78-fold greater affinity for the delta opioid receptor than the mu receptor and there was no binding to the kappa opioid receptor. BBI-11008 (3.2 – 100; 10 – 32 mg/kg, i.v.) and morphine (1 – 10; 1 – 3.2 mg/kg, i.v.) produced antinociceptive and anti-allodynic effects in assays of acute thermal nociception and complete Freund’s adjuvant (CFA)-induced inflammatory pain, with BBI-11008 being less potent than morphine in both assays. BBI-11008 (1 – 18 mg/kg, i.v.) had similar efficacy to gabapentin (10 – 56 mg/kg, i.v.) in a spinal nerve ligation (SNL) model of neuropathic pain. In the respiration assay, with increasing %CO2 exposure, BBI-11008 produced an initial increase (32 mg/kg, s.c.) and then decrease (56 mg/kg, s.c.) in minute volume (MV) whereas morphine (3.2 – 32 mg/kg, s.c.) produced dose-dependent decreases in MV. In the drug self-administration procedure, BBI-11008 did not maintain self-administration at any dose tested. These results suggest that the glycopeptide drug candidate possesses broad-spectrum antinociceptive and anti-allodynic activity across a range of pain-like conditions. Relative to morphine or fentanyl, the profile for BBI-11008 in the respiration and drug self-administration assays suggests that BBI-11008 may have less pronounced deleterious side effects. Continued assessment of this compound is warranted.
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影响因子：
4.2
作者：
Li Y;Lefever MR;Muthu D;Bidlack JM;Bilsky EJ;Polt R
通讯作者：
Polt R
DOI：
10.1124/jpet.104.069393
发表时间：
2004-10-01
影响因子：
3.5
作者：
Elmagbari, NO;Egleton, RD;Bilsky, EJ
通讯作者：
Bilsky, EJ
影响因子：
7.3
作者：
Bilsky, EJ;Egleton, RD;Polt, R
通讯作者：
Polt, R
影响因子：
5.3
作者：
Colburn, RW;Rickman, AJ;DeLeo, JA
通讯作者：
DeLeo, JA
影响因子：
37.8
作者：
Antman, Elliott M.
通讯作者：
Antman, Elliott M.