A Brief Survey on Recent Endomorphin-1 and Endomorphin-2 Analogues

Abstract

The neurophysiological distribution of the Endomorphins (EMs), i.e., Endomorphin-1 (EM1) and Endomorphin-2 (EM2), reflects their potential role in many major biological processes. These include perception of pain, responses related to stress, and complex functions such as reward, arousal, and vigilance, as well as autonomic, cognitive, neuroendocrine, and limbic homeostasis. In particular, EM1 and EM2 have demonstrated potent antinociception without some of the undesired side effects of opiate drugs. Unfortunately, their clinical applications as painkillers remain unrealistic due to their poor metabolic stability, inability to cross the Blood-Brain Barrier (BBB), and efficient efflux. In this review is reported a brief collection of recently published modified endomorphins, for which the potentiality as painkiller was clearly demonstrated in vitro and in vivo. Selected structures of bioactive EM analogues highlighting the modified residues, with references, are reported in the table of the review.