Gonçalves Jacqueline, Rangel Marisa, Biolchi Andréia, Alves Eveline, Moreira Karla, Silva Luciano, Mortari Márcia
Laboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília-DF, 70910-900, Brazil.
Laboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília-DF, 70910-900, Brazil; Immunopathology Laboratory, Butantan Institute, Sao Paulo, Brazil.
Toxicon. 2016 Sep 15;120:15-21. doi: 10.1016/j.toxicon.2016.07.009. Epub 2016 Jul 12.
Analgesic therapy is based on the sequential treatment of pain, in which opioids are drugs of last resource and known to be highly effective, but are also responsible for undesirable side effects, tolerance and addiction. There is a need for new drugs with alternative targets in order to minimize side effects and improve treatment efficacy. Mastoparans are an abundant class of peptides in wasp venom and have shown great potential as new drugs, as well as being excellent tools for the study of G-protein-coupled receptors. The objective of this study was to investigate the antinociceptive activity of the mastoparan Agelaia-MP I and the mechanisms involved. Agelaia-MP I (MW 1565 Da) showed dose-dependent antinociceptive activity in mice submitted to i.c.v. injection in two different models. The highest dose produced a maximum effect for up to 4 h, and nociception remained low three days after injection. Further experiments showed that Agelaia-MPI induced partial and reversible blockade of the amplitude of action potential, probably interacting with voltage-gated sodium channels. These results revealed the significant potential impact of compounds isolated from wasp venom on the central nervous system (CNS). In addition, the antinociceptive effect described here is a novel activity for mastoparans.
镇痛疗法基于对疼痛的序贯治疗，其中阿片类药物是最后的治疗手段，已知其疗效显著，但也会导致不良副作用、耐受性和成瘾性。需要有具有替代靶点的新药，以尽量减少副作用并提高治疗效果。马斯托帕兰是黄蜂毒液中一类丰富的肽，已显示出作为新药的巨大潜力，也是研究G蛋白偶联受体的优秀工具。本研究的目的是研究马斯托帕兰Agelaia-MP I的抗伤害感受活性及其相关机制。Agelaia-MP I（分子量1565 Da）在两种不同模型中对经脑室内注射的小鼠显示出剂量依赖性抗伤害感受活性。最高剂量产生的最大效应可持续4小时，注射三天后伤害感受仍维持在较低水平。进一步的实验表明，Agelaia-MPI诱导动作电位幅度的部分和可逆性阻断，可能与电压门控钠通道相互作用。这些结果揭示了从黄蜂毒液中分离出的化合物对中枢神经系统（CNS）的重大潜在影响。此外，这里描述的抗伤害感受作用是马斯托帕兰的一种新活性。
