Opioid Peptides--Molecular Mechanism Of Action

整个研究包括对一种有效的双Mu/Delta阿片受体拮抗剂H-DMT-Tic-Lys-NH-CH2-Ph(MZ-2)的研究。双作用DMT-Tic药典化合物具有较高的阿片受体亲和力(Kiδ1 nM，Ki mu4 nM)。含有疏水基团的非带电C末端和Lys残基的存在是被u-阿片受体识别所必需的。在肥胖(ob/ob mine)和饮食诱导肥胖小鼠模型中口服MZ-2，其中包含时间释放的Azlet迷你泵，以持续供应药物，以减少体重增加，增加肥胖和瘦小鼠的夜间活动，增强骨骼矿物质沉积，并对血清激素和血糖水平产生积极影响。数据证明，这种名为MZ-2的药物可以通过增加30%的骨矿沉积来改善导致肥胖的各种因素，并缓解骨质疏松症的症状。这种独特的分子具有潜在的应用来对抗人类疾病状态，涉及大脑中的神经元奖励机制：双重u/Delta阿片类拮抗剂可能适用于治疗多种疾病状态。

The overall study encompassed research on an effective dual mu-/delta-opioid receptor antagonist, H-Dmt-Tic-Lys-NH-CH2-Ph (MZ-2). The dual acting Dmt-Tic pharmacophoric compound exhibited high opioid receptor affinity (Ki delta < 1 nM, Ki mu 4 nM). The non-charged C-terminus containing a hydrophobic group and the presence of a Lys residue are required for recognition by the mu-opioid receptor. Oral administration of MZ-2 in a mouse model of obesity (ob/ob mine) and diet-induced obesity in mice containing a time-released Azlet mini-pumps to continually supply the drug in order to reduce body weight gain, increase nocturnal activity in both obese and lean mice, enhance bone mineral deposition and produce positive effects on serum hormones and glucose levels. The data verify that this drug, MZ-2, could ameliorate various factors contributing to obesity and alleviate symptoms of osteoporosis by enhancing bone mineral deposition by 30%. This unique molecule has the potential application to combat human disease states involving the neuronal reward mechanism in the brain: dual mu-/delta-opioid antagonists could be applicable in treatment of numerous disease states.