Roques Bernard P
Membre de l'Académie des Sciences (France et Europe), U1022 INSERM/UMR 8258 CNRS, Université Paris-Descartes (Paris V), CSO Pharmaleads SAS, 4 Avenue de l'Observatoire, 75006, Paris, France.
Handb Exp Pharmacol. 2018;247:53-70. doi: 10.1007/164_2016_17.
Very few discoveries in the neurosciences have triggered clinical speculation and experimentation regarding the etiology of psychiatric illness to the same extent as that following identification of the opiate receptor(s) and subsequent isolation of endogenous morphine-like peptides. There is overwhelming evidence in animals and in human that opioids are involved in behaviorally relevant issues such as the modulation of pain, the response to stress, motivation, addiction, sexuality, food intake, etc., but our knowledge on the possible relation between opioids and mental illness is still very limited.These responses could be explored eitheir by using higlhy selective delta agonist or by emphasizing the effects of phasically secreted endogenous opioid peptides, enkephalin. Both approaches were investigated in particular through protection of enkephalin degradation by dual enkephalinase ihibitors DENKIs such as RB101, PL37 or PL265.
在神经科学领域,很少有发现能像确定阿片受体以及随后分离内源性吗啡样肽那样,在同等程度上引发关于精神疾病病因的临床推测和实验。在动物和人类中,有压倒性的证据表明阿片类物质参与了与行为相关的问题,如疼痛调节、应激反应、动机、成瘾、性行为、食物摄入等,但我们对阿片类物质与精神疾病之间可能关系的了解仍然非常有限。这些反应可以通过使用高度选择性的δ激动剂或强调阶段性分泌的内源性阿片肽脑啡肽的作用来进行探索。特别是通过双重脑啡肽酶抑制剂(DENKIs)如RB101、PL37或PL265保护脑啡肽降解,对这两种方法进行了研究。