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Neurotransmitters and pharmacology
Published in Mark J. Ashley, David A. Hovda, Traumatic Brain Injury, 2017
Ronald A. Browning, Richard W. Clough
The first discovered opioid peptides were the pentapeptides (containing five amino acids), leucine-enkephalin, and methionine-enkephalin, which were isolated by Hughes et al.202 Although there may be other families of opioid peptides, current interest is focused on three separate families of opioid peptides, each derived from a separate gene family.203 These include 1) the enkephalins (pentapeptides derived from a proenkephalin precursor), 2) the endorphins (e.g., β-endorphin, a 31 amino acid-containing peptide derived from proopiomelanocortin or POMC), and 3) the dynorphins (8 to 13 amino acid-containing peptides derived from a prodynorphin precursor). Three other endogenous opioid peptides have more recently been discovered and are known as orphanin FQ, endomorphin-1, and endomorphin-2. Orphanin FQ, also known as nociceptin, has effects opposite those of morphine and is referred to as pronociceptive (see section on opioid receptors). Much current research is focused on whether the endormorphins are selective mu agonists, but because there is relatively little known about the edomorphin peptides, we focus our discussion on the enkephalins, endorphins, and dynorphins.
Clinical pharmacology: opioids
Published in Pamela E Macintyre, Suellen M Walker, David J Rowbotham, Clinical Pain Management, 2008
David J Rowbotham, Alcira Serrano-Gomez, Anne Heffernan
Endogenous ligands acting at opioid receptors include enkephalins (δ receptor), dynorphins (κ receptor), endorphins (high affinity, but poor selectivity for μ receptors),41 and nociceptin/orphanin FQ (NOP receptor, see below under Nociceptin/orphanin FQ receptor). The endogenous selective ligands for the μ receptor (endomorphins) were first identified in 1997.29 Both endomorphin 1 and endomorphin 2 are peptides of four amino acids and intimately involved in nociceptive pathways.42 Unlike the other recognized peptides, precursors for endomorphin 1 and 2 have not been identified.
Antinociceptive potency of a fluorinated cyclopeptide Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Justyna Piekielna-Ciesielska, Adriano Mollica, Stefano Pieretti, Jakub Fichna, Agata Szymaszkiewicz, Marta Zielińska, Radzisław Kordek, Anna Janecka
Anti-nociception was studied in the hot-plate test in mice after i.c.v. or i.v. administration of peptides. The results obtained in the dose-response studies after i.c.v. administration are shown in Figure 1(A). Both tested compounds showed dose-dependent anti-nociceptive activity, significantly stronger than that of endomorphin-2 (EM-2). The ED50 values (jumping response) for C-36 and F-81 were 57.78 and 17.27 ng, respectively, indicating that F-81 was approximately threefold more potent than C-36 (Figure 1(A)). In order to investigate if these peptides are able to cross the BBB, peripheral i.v. administration of the peptides was performed, and the results are reported in Figure 1(B). After i.v. administration at the dose of 20 mg/kg, only a negligible anti-nociceptive activity was observed for both compounds (Figure 1(B)). To characterize the involvement of opioid receptors in the anti-nociceptive action of analog F-81, co-administration studies with opioid receptor antagonists were performed. The anti-nociceptive effect of F-81 (10 ng/animal, i.c.v.) was blocked by β-funaltrexamine (β-FNA, 1 µg/animal), showing the involvement of the mu opioid receptors. The delta-opioid receptor antagonist, naltrindole (NTL, 1 µg/animal), and kappa-opioid receptor antagonist, norbinaltorphimine (nor-BNI, 5 µg/animal, i.c.v.), did not modify the anti-nociceptive action of F-81 (Figure 1(C)). Even though F-81 and C-36 showed significant kappa-affinity, the obtained results are in agreement with a generally accepted fact that the anti-nociceptive effects are mainly mediated by the mu opioid receptor32,38.