title: Original endomorphin-1 analogues exhibit good analgesic effects with minimal implications for human sperm motility.
abstract: To search a novel analgesic characterizes the effects on human sperm motility as minimal as possible. A new class of endomorphin-1 (EM-1) analogues was synthesized by combining successful chemical modifications including N-terminal guanidino modification, Phe4was chlorinated, replaced of l-Pro2-Trp3by d-Ala2-Gly3or d-Pro2-Gly3at position 2 and 3. Their bioactivities were measured by radioligand binding assay, metabolic stability, antinociception activity and sperm motility effects. In radioligand binding assays, analogue GAGP shown a μ-opioid receptor affinity about 17.7-fold higher and a 57.3-fold higher δ-opioid receptor affinity than EM-1. In the metabolic stability assays, GAGP had the longest half-lives and 16.6-fold higher than EM-1. In the tail-flick test in mice, GAGP showed the best analgesia. In sperm motility assays, the group of GAGP (10-5, 10-7mol/L) decreased of the percentage of a+b grade, and no significant when compared with initial value. In GAGP (10-6mol/L) group, sperm motility was progressively increased, although it was not statistically significant. But at the groups of morphine (10-7mol/L) and GAGD (10-7mol/L), these caused significant reduction between 0 and 90 min. We found that analogues GAGP, activating μ-opioid receptor and partial δ-opioid receptor, exhibit good analgesic effects with minimal implications for human sperm motility. It might be important in potential application as drug candidates of analgesic without implications for human sperm motility.
authors.affiliation: The Reproductive Medicine Special Hospital of the First Hospital of Lanzhou University, Key Laboratory for Reproductive Medicine and Embryo Gansu Province, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Reproductive Medicine Special Hospital of the First Hospital of Lanzhou University, Key Laboratory for Reproductive Medicine and Embryo Gansu Province, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: The Reproductive Medicine Special Hospital of the First Hospital of Lanzhou University, Key Laboratory for Reproductive Medicine and Embryo Gansu Province, China.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Gao
authors.affiliation: The Reproductive Medicine Special Hospital of the First Hospital of Lanzhou University, Key Laboratory for Reproductive Medicine and Embryo Gansu Province, China.
authors.forename: Yongan
authors.initials: Y
authors.lastname: Gan
authors.affiliation: The Reproductive Medicine Special Hospital of the First Hospital of Lanzhou University, Key Laboratory for Reproductive Medicine and Embryo Gansu Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Reproductive Medicine Special Hospital of the First Hospital of Lanzhou University, Key Laboratory for Reproductive Medicine and Embryo Gansu Province, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: The Reproductive Medicine Special Hospital of the First Hospital of Lanzhou University, Key Laboratory for Reproductive Medicine and Embryo Gansu Province, China.
authors.forename: Junping
authors.initials: J
authors.lastname: Hu
authors.affiliation: The Reproductive Medicine Special Hospital of the First Hospital of Lanzhou University, Key Laboratory for Reproductive Medicine and Embryo Gansu Province, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Ma
authors.affiliation: The Reproductive Medicine Special Hospital of the First Hospital of Lanzhou University, Key Laboratory for Reproductive Medicine and Embryo Gansu Province, China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Wu
authors.affiliation: The Reproductive Medicine Special Hospital of the First Hospital of Lanzhou University, Key Laboratory for Reproductive Medicine and Embryo Gansu Province, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Ma
authors.affiliation: The Reproductive Medicine Special Hospital of the First Hospital of Lanzhou University, Key Laboratory for Reproductive Medicine and Embryo Gansu Province, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Liang
authors.affiliation: The Reproductive Medicine Special Hospital of the First Hospital of Lanzhou University, Key Laboratory for Reproductive Medicine and Embryo Gansu Province, China. Electronic address: zhangxuehong2016@163.com.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D006207:Half-Life; D006801:Humans; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D017465:Receptors, Opioid, delta / Q000737:chemistry / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000737:chemistry / Q000378:metabolism; D013081:Sperm Motility / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C105293:endomorphin 1
keywords: Analgesic; Endomorphin-1 analogues; Sperm motility