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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

δ Opioid Receptor Inverse Agonists and their In Vivo Pharmacological Effects

Author(s): Shigeto Hirayama and Hideaki Fujii*

Volume 20, Issue 31, 2020

Page: [2889 - 2902] Pages: 14

DOI: 10.2174/1568026620666200402115654

Price: $65


The discovery of δ opioid receptor inverse agonist activity induced by ICI-174,864, which was previously reported as an δ opioid receptor antagonist, opened the door for the investigation of inverse agonism/constitutive activity of the receptors. Various peptidic or non-peptidic δ opioid receptor inverse agonists have since been developed. Compared with the reports dealing with in vitro inverse agonist activities of novel compounds or known compounds as antagonists, there have been almost no publications describing the in vivo pharmacological effects induced by a δ opioid receptor inverse agonist. After the observation of anorectic effects with the δ opioid receptor antagonism was discussed in the early 2000s, the short-term memory improving effects and antitussive effects have been very recently reported as possible pharmacological effects induced by a δ opioid receptor inverse agonist. In this review, we will survey the developed δ opioid receptor inverse agonists and summarize the possible in vivo pharmacological effects by δ opioid receptor inverse agonists. Moreover, we will discuss important issues involved in the investigation of the in vivo pharmacological effects produced by a δ opioid receptor inverse agonist.

Keywords: δ Opioid receptor, Constitutive activity, Inverse agonist, Neutral antagonist, Anorectic effect, Short-term memory improving effect, Antitussive effect.

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Leff, P. The two-state model of receptor activation. Trends Pharmacol. Sci., 1995, 16(3), 89-97.
[] [PMID: 7540781]
Costa, T.; Herz, A. Antagonists with negative intrinsic activity at δ opioid receptors coupled to GTP-binding proteins. Proc. Natl. Acad. Sci. USA, 1989, 86(19), 7321-7325.
[] [PMID: 2552439]
Kenakin, T. Efficacy as a vector: the relative prevalence and paucity of inverse agonism. Mol. Pharmacol., 2004, 65(1), 2-11.
[] [PMID: 14722230]
Milligan, G. Constitutive activity and inverse agonists of G protein-coupled receptors: a current perspective. Mol. Pharmacol., 2003, 64(6), 1271-1276.
[] [PMID: 14645655]
Meneses, A. Could the 5-HT1B receptor inverse agonism affect learning consolidation? Neurosci. Biobehav. Rev., 2001, 25(2), 193-201.
[] [PMID: 11323083]
Kenakin, T. Inverse, protean, and ligand-selective agonism: matters of receptor conformation. FASEB J., 2001, 15(3), 598-611.
[] [PMID: 11259378]
Chavkin, C.; McLaughlin, J.P.; Celver, J.P. Regulation of opioid receptor function by chronic agonist exposure: constitutive activity and desensitization. Mol. Pharmacol., 2001, 60(1), 20-25.
[] [PMID: 11408596]
Teitler, M.; Herrick-Davis, K.; Purohit, A. Constitutive activity of G-protein coupled receptors: emphasis on serotonin receptors. Curr. Top. Med. Chem., 2002, 2(6), 529-538.
[] [PMID: 12052192]
Leurs, R.; Church, M.K.; Taglialatela, M. H1-antihistamines: inverse agonism, anti-inflammatory actions and cardiac effects. Clin. Exp. Allergy, 2002, 32(4), 489-498.
[] [PMID: 11972592]
Gurdal, H. Inverse agonism at β-adrenergic receptors: therapeutic implications. Expert Rev. Neurother., 2002, 2(2), 261-269.
[] [PMID: 19811007]
Seifert, R.; Wenzel-Seifert, K. Constitutive activity of G-protein-coupled receptors: cause of disease and common property of wild-type receptors. Naunyn Schmiedebergs Arch. Pharmacol., 2002, 366(5), 381-416.
[] [PMID: 12382069]
Vargo, E.V.; Hosohata, K.; Hosohata, Y.; Tsang, J.; Burkey, T.; Alfaro-Lopez, J.; Tang, X.; Hruby, V.J.; Roeske, W.R.; Yamamura, H.I. Inverse agonism at the delta opioid receptors.The Delta Receptor; Chang, K.J.; Porreca, F.; Woods, J.H., Eds.; Marcel Dekker, Inc.: New York, 2003, pp. 211-230.
Costa, T.; Cotecchia, S. Historical review: Negative efficacy and the constitutive activity of G-protein-coupled receptors. Trends Pharmacol. Sci., 2005, 26(12), 618-624.
[] [PMID: 16260046]
Berg, K.A.; Harvey, J.A.; Spampinato, U.; Clarke, W.P. Physiological relevance of constitutive activity of 5-HT2A and 5-HT2C receptors. Trends Pharmacol. Sci., 2005, 26(12), 625-630.
[] [PMID: 16269190]
Sadée, W.; Wang, D.; Bilsky, E.J. Basal opioid receptor activity, neutral antagonists, and therapeutic opportunities. Life Sci., 2005, 76(13), 1427-1437.
[] [PMID: 15680308]
Bond, R.A.; Ijzerman, A.P. Recent developments in constitutive receptor activity and inverse agonism, and their potential for GPCR drug discovery. Trends Pharmacol. Sci., 2006, 27(2), 92-96.
[] [PMID: 16406086]
Arrang, J.M.; Morisset, S.; Gbahou, F. Constitutive activity of the histamine H3 receptor. Trends Pharmacol. Sci., 2007, 28(7), 350-357.
[] [PMID: 17573125]
Tao, Y.X. Constitutive activation of G protein-coupled receptors and diseases: insights into mechanisms of activation and therapeutics. Pharmacol. Ther., 2008, 120(2), 129-148.
[] [PMID: 18768149]
Berg, K.A.; Harvey, J.A.; Spampinato, U.; Clarke, W.P. Physiological and therapeutic relevance of constitutive activity of 5-HT2A and 5-HT2C receptors for the treatment of depression. Di Giovanni, G.; Di Matteo,V.; Esposito, E., EDs; Progress in Brain Research. Elsevier B.V.: Amsterdam, , 2008; 172, pp. 287-305.
[] [PMID: 18772038]
Yasuda, N.; Akazawa, H.; Qin, Y.; Zou, Y.; Komuro, I. A novel mechanism of mechanical stress-induced angiotensin II type 1-receptor activation without the involvement of angiotensin II. Naunyn Schmiedebergs Arch. Pharmacol., 2008, 377(4-6), 393-399.
[] [PMID: 18046542]
Aloyo, V.J.; Berg, K.A.; Spampinato, U.; Clarke, W.P.; Harvey, J.A. Current status of inverse agonism at serotonin2A (5-HT2A) and 5-HT2C receptors. Pharmacol. Ther., 2009, 121(2), 160-173.
[] [PMID: 19109993]
Aloyo, V.J.; Berg, K.A.; Clarke, W.P.; Spampinato, U.; Harvey, J.A. Inverse agonism at serotonin and cannabinoid receptors. Prog. Mol. Biol. Transl. Sci; Lunn, C.A., Ed.; Elsevier B.V: Amsterdam,, 2010, 91, pp. 1-40.
[] [PMID: 20691957]
Lunn, C.A. Updating the chemistry and biology of cannabinoid CB2 receptor-specific inverse agonists. Curr. Top. Med. Chem., 2010, 10(8), 768-778.
[] [PMID: 20370714]
Kachaylo, E.M.; Pustylnyak, V.O.; Lyakhovich, V.V.; Gulyaeva, L.F. Constitutive androstane receptor (CAR) is a xenosensor and target for therapy. Biochemistry (Mosc.), 2011, 76(10), 1087-1097.
[] [PMID: 22098234]
Khilnani, G.; Khilnani, A.K. Inverse agonism and its therapeutic significance. Indian J. Pharmacol., 2011, 43(5), 492-501.
[] [PMID: 22021988]
Navailles, S.; Lagière, M.; Guthrie, M.; De Deurwaerdère, P. Serotonin2c receptor constitutive activity: in vivo direct and indirect evidence and functional significance. Cent. Nerv. Syst. Agents Med. Chem., 2013, 13(2), 98-107.
[] [PMID: 23441866]
Park, P.S.H. Constitutively active rhodopsin and retinal disease. Adv. Pharmacol., 2014, 70, 1-36.
[ PMID:24931191]
Ulloa-Aguirre, A.; Reiter, E.; Bousfield, G.; Dias, J.A.; Huhtaniemi, I. Constitutive activity in gonadotropin receptors. Adv. Pharmacol., 2014, 70, 37-80.
[ PMID:24931192]
Kleinau, G.; Biebermann, H. Constitutive activities in the thyrotropin receptor: regulation and significance.Advances in Pharmacology, Tao, Y.X; Academic press: New York, 2014, pp. 81-119.
[ PMID:24931193]
Fong, T.M. Constitutive activity in cannabinoid receptors.Advances in Pharmacology; Tao, Y.X., Ed.; Academic press: New York, 2014, pp. 121-133.
Tao, Y.X. Constitutive activity in melanocortin-4 receptor: biased signaling of inverse agonists. In: Advances.; Pharmacology, Y.X., Ed.; Academic press. New York, 2014, pp. 135-154.
[ PMID:24931195]
Unal, H.; Karnik, S.S. Constitutive activity in the angiotensin II type 1 receptor: discovery and applications.Advances in Pharmacology; Tao, Y.X., Ed.; Academic press: New York, 2014, pp. 155-174.
[ PMID:24931196]
Zhang, B.; Albaker, A.; Plouffe, B.; Lefebvre, C.; Tiberi, M. Constitutive activities and inverse agonism in dopamine receptors. In: Advances in Pharmacology; Tao, Y.X., Ed.; Academic press: New York,, 2014, 70, pp. 175-214.
[] [PMID: 24931197]
Flanagan, C.A. Receptor conformation and constitutive activity in CCR5 chemokine receptor function and HIV infection. In: Advances in Pharmacology; Tao, Y.X., Ed.; Academic press: New York, 2014, 70, pp. 215-263.
[] [PMID: 24931198]
Han, X. Constitutively active chemokine CXC receptors. Advances in Pharmacology; Tao, Y.X., Ed.; Academic press: New York, 2014, 70, pp. 265-301.
[] [PMID: 24931199]
Pydi, S.P.; Bhullar, R.P.; Chelikani, P. Constitutive activity of bitter taste receptors (T2Rs). In: Advances in Pharmacology; Tao, Y.X., Ed.; Academic press: New York, , 2014; 70, pp. 303-326.
[] [PMID: 24931200]
Chan, S.C.; Dehm, S.M. Constitutive activity of the androgen receptor. . In: Advances in Pharmacology; Tao, Y.X., Ed.; Academic press: New York,, 2014, 70, pp. 327-366.
[] [PMID: 24931201]
Miller, D.; Wang, L.; Zhong, J. Sodium channels, cardiac arrhythmia, and therapeutic strategy. In: Advances in Pharmacology; Tao, Y.X., Ed.; Academic press: New York, 2014, 70, pp. 367-392.
[] [PMID: 24931202]
Voigt, N.; Abu-Taha, I.; Heijman, J.; Dobrev, D. Constitutive activity of the acetylcholine-activated potassium current IK, ACh. in cardiomyocytes. In: Advances in Pharmacology; Tao, Y.X., Ed.; Academic press: New York , 2014; 70, pp. 393-409.
[ ] [PMID: 24931203]
Berg, K.A.; Clarke, W.P. Making sense of pharmacology: inverse agonism and functional selectivity. Int. J. Neuropsychopharmacol., 2018, 21(10), 962-977.
[] [PMID: 30085126]
Cotton, R.; Giles, M.G.; Miller, L.; Shaw, J.S.; Timms, D. ICI 174864: a highly selective antagonist for the opioid δ-receptor. Eur. J. Pharmacol., 1984, 97(3-4), 331-332.
[] [PMID: 6323195]
Beddell, C.R.; Clark, R.B.; Lowe, L.A.; Wilkinson, S.; Chang, K-J.; Cuatrecasas, P.; Miller, R. A conformational analysis for leucine-enkephalin using activity and binding data of synthetic analogues. Br. J. Pharmacol., 1977, 61(3), 351-356.
[] [PMID: 201319]
Pfeiffer, A.; Herz, A. Enhancement of δ- but not μ-opiate agonist binding by calcium. Naunyn Schmiedebergs Arch. Pharmacol., 1982, 319(2), 147-153.
[] [PMID: 6287305]
Mullaney, I.; Carr, I.C.; Milligan, G. Analysis of inverse agonism at the δ opioid receptor after expression in Rat 1 fibroblasts. Biochem. J., 1996, 315(Pt 1), 227-234.
[] [PMID: 8670111]
Katada, T.; Ui, M. ADP ribosylation of the specific membrane protein of C6 cells by islet-activating protein associated with modification of adenylate cyclase activity. J. Biol. Chem., 1982, 257(12), 7210-7216.
[PMID: 7200979]
Portoghese, P.S.; Sultana, M.; Nagase, H.; Takemori, A.E. Application of the message-address concept in the design of highly potent and selective non-peptide δ opioid receptor antagonists. J. Med. Chem., 1988, 31(2), 281-282.
[] [PMID: 2828619]
Portoghese, P.S.; Sultana, M.; Takemori, A.E. Naltrindole, a highly selective and potent non-peptide δ opioid receptor antagonist. Eur. J. Pharmacol., 1988, 146(1), 185-186.
[] [PMID: 2832195]
Portoghese, P.S.; Sultana, M.; Takemori, A.E. Design of peptidomimetic δ opioid receptor antagonists using the message-address concept. J. Med. Chem., 1990, 33(6), 1714-1720.
[] [PMID: 2160538]
Chiu, T.T.; Yung, L.Y.; Wong, Y.H. Inverse agonistic effect of ICI-174,864 on the cloned δ-opioid receptor: role of G protein and adenylyl cyclase activation. Mol. Pharmacol., 1996, 50(6), 1651-1657.
[PMID: 8967989]
Merkouris, M.; Mullaney, I.; Georgoussi, Z.; Milligan, G. Regulation of spontaneous activity of the δ-opioid receptor: studies of inverse agonism in intact cells. J. Neurochem., 1997, 69(5), 2115-2122.
[] [PMID: 9349557]
Neilan, C.L.; Akil, H.; Woods, J.H.; Traynor, J.R. Constitutive activity of the δ-opioid receptor expressed in C6 glioma cells: identification of non-peptide δ-inverse agonists. Br. J. Pharmacol., 1999, 128(3), 556-562.
[] [PMID: 10516632]
Liu, J.G.; Prather, P.L. Chronic agonist treatment converts antagonists into inverse agonists at δ-opioid receptors. J. Pharmacol. Exp. Ther., 2002, 302(3), 1070-1079.
[] [PMID: 12183665]
Tryoen-Tóth, P.; Décaillot, F.M.; Filliol, D.; Befort, K.; Lazarus, L.H.; Schiller, P.W.; Schmidhammer, H.; Kieffer, B.L. Inverse agonism and neutral antagonism at wild-type and constitutively active mutant delta opioid receptors. J. Pharmacol. Exp. Ther., 2005, 313(1), 410-421.
[] [PMID: 15590769]
Liao, S.; Lin, J.; Shenderovich, M.D.; Han, Y.; Hasohata, K.; Davis, P.; Qiu, W.; Porrece, F.; Yamamura, H.I.; Hruby, V.J. The stereochemical requirements of the novel δ-opioid selective dipeptide antagonist TMT-Tic. Bioorg. Med. Chem. Lett., 1997, 7, 3049-3052.
Hosohata, K.; Burkey, T.H.; Alfaro-Lopez, J.; Hruby, V.J.; Roeske, W.R.; Yamamura, H.I. (2S,3R)TMT-L-Tic-OH is a potent inverse agonist at the human δ-opioid receptor. Eur. J. Pharmacol., 1999, 380(1), R9-R10.
[] [PMID: 10513562]
Hosohata, K.; Varga, E.V.; Alfaro-Lopez, J.; Tang, X.; Vanderah, T.W.; Porreca, F.; Hruby, V.J.; Roeske, W.R.; Yamamura, H.I. (2S,3R)β-methyl-2′,6′-dimethyltyrosine-L-tetrahydroisoquinoline-3-carboxylic acid [(2S,3R)TMT-L-Tic-OH] is a potent, selective δ-opioid receptor antagonist in mouse brain. J. Pharmacol. Exp. Ther., 2003, 304(2), 683-688.
[] [PMID: 12538822]
Schiller, P.W.; Nguyen, T.M-D.; Weltrowska, G.; Wilkes, B.C.; Marsden, B.J.; Lemieux, C.; Chung, N.N. Differential stereochemical requirements of μ vs. δ opioid receptors for ligand binding and signal transduction: development of a class of potent and highly δ-selective peptide antagonists. Proc. Natl. Acad. Sci. USA, 1992, 89(24), 11871-11875.
[] [PMID: 1334552]
Martin, N.A.; Ruckle, M.B.; VanHoof, S.L.; Prather, P.L. Agonist, antagonist, and inverse agonist characteristics of TIPP (H-Tyr-Tic-Phe-Phe-OH), a selective δ-opioid receptor ligand. J. Pharmacol. Exp. Ther., 2002, 301(2), 661-671.
[] [PMID: 11961071]
Leff, P. Inverse agonism: theory and practice. Trends Pharmacol. Sci., 1995, 16(8), 256-258.
[] [PMID: 7482981]
Schramm, M.; Rodbell, M. A persistent active state of the adenylate cyclase system produced by the combined actions of isoproterenol and guanylyl imidodiphosphate in frog erythrocyte membranes. J. Biol. Chem., 1975, 250(6), 2232-2237.
[PMID: 163823]
Lefkowitz, R.J.; Caron, M.G. Characteristics of 5′-guanylyl imidodiphosphate-activated adenylate cyclase. J. Biol. Chem., 1975, 250(12), 4418-4422.
[PMID: 166994]
Salvadori, S.; Attila, M.; Balboni, G.; Bianchi, C.; Bryant, S.D.; Crescenzi, O.; Guerrini, R.; Picone, D.; Tancredi, T.; Temussi, P.A.; Lazarus, L.H. δ opioidmimetic antagonists: prototypes for designing a new generation of ultraselective opioid peptides. Mol. Med., 1995, 1(6), 678-689.
[] [PMID: 8529134]
Bryant, S.D.; Salvadori, S.; Cooper, P.S.; Lazarus, L.H. New δ-opioid antagonists as pharmacological probes. Trends Pharmacol. Sci., 1998, 19(2), 42-46.
[] [PMID: 9550939]
Salvadori, S.; Balboni, G.; Guerrini, R.; Tomatis, R.; Bianchi, C.; Bryant, S.D.; Cooper, P.S.; Lazarus, L.H. Evolution of the Dmt-Tic pharmacophore: N-terminal methylated derivatives with extraordinary δ opioid antagonist activity. J. Med. Chem., 1997, 40(19), 3100-3108.
[] [PMID: 9301674]
Lazarus, L.H.; Bryant, S.D.; Cooper, P.S.; Guerrini, R.; Balboni, G.; Salvadori, S. Design of δ-opioid peptide antagonists for emerging. Drug Discov. Today, 1998, 3, 284-294.
Labarre, M.; Butterworth, J.; St-Onge, S.; Payza, K.; Schmidhammer, H.; Salvadori, S.; Balboni, G.; Guerrini, R.; Bryant, S.D.; Lazarus, L.H. Inverse agonism by Dmt-Tic analogues and HS 378, a naltrindole analogue. Eur. J. Pharmacol., 2000, 406(1), R1-R3.
[] [PMID: 11011049]
Carroll, F.I.; Zhang, L.; Mascarella, S.W.; Navarro, H.A.; Rothman, R.B.; Cantrell, B.E.; Zimmerman, D.M.; Thomas, J.B. Discovery of the first N-substituted 4β-methyl-5-(3-hydroxyphenyl)morphan to possess highly potent and selective opioid δ receptor antagonist activity. J. Med. Chem., 2004, 47(2), 281-284.
[] [PMID: 14711299]
Thomas, J.B.; Zhang, L.; Navarro, H.A.; Carroll, F.I. Highly potent and selective phenylmorphan-based inverse agonists of the opioid δ receptor. J. Med. Chem., 2006, 49(18), 5597-5609.
[] [PMID: 16942033]
Cheng, K.; Kim, I.J.; Lee, M-J.; Adah, S.A.; Raymond, T.J.; Bilsky, E.J.; Aceto, M.D.; May, E.L.; Harris, L.S. Coop, A.; Dersch, C.M.; Rothman, R.B.; Jacobson, A.E.; Rice, K.C. Opioid ligands with mixed properties from substituted enantiomeric N-phenetyl-5-phenylmorphans. synthesis of a δ-agonist δ-antagonist and δ- inverse agonist. Org. Biomol. Chem., 2007, 5, 1177-1190.
[] [PMID: 17406716]
Shaw, W.N. Long-term treatment of obese Zucker rats with LY255582 and other appetite suppressants. Pharmacol. Biochem. Behav., 1993, 46(3), 653-659.
[] [PMID: 8278442]
Emmerson, P.J.; McKinzie, J.H.; Surface, P.L.; Suter, T.M.; Mitch, C.H.; Statnick, M.A. Na+ modulation, inverse agonism, and anorectic potency of 4-phenylpiperidine opioid antagonists. Eur. J. Pharmacol., 2004, 494(2-3), 121-130.
[] [PMID: 15212965]
Zaki, P.A.; Keith, D.E., Jr; Thomas, J.B.; Carroll, F.I.; Evans, C.J. Agonist-, antagonist-, and inverse agonist-regulated trafficking of the δ-opioid receptor correlates with, but does not require, G protein activation. J. Pharmacol. Exp. Ther., 2001, 298(3), 1015-1020.
[PMID: 11504798]
Thomas, J.B.; Mascarella, S.W.; Rothman, R.B.; Partilla, J.S.; Xu, H.; McCullough, K.B.; Dersch, C.M.; Cantrell, B.E.; Zimmerman, D.M.; Carroll, F.I. Investigation of the N-substituent conformation governing potency and μ receptor subtype-selectivity in (+)-(3R, 4R)-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists. J. Med. Chem., 1998, 41(11), 1980-1990.
[] [PMID: 9599247]
Schmidhammer, H.; Krassnig, R.; Greiner, E.; Schultz, J.; White, A.; Berzetei-Gurske, I.P. Synthesis and biological evaluation of 14-alkoxymorphinans: part 15. Novel δ opioid receptor antagonists with high affinity and selectivity in the 14-alkoxy-substituted indolomorphinan series. Helv. Chim. Acta, 1998, 81, 1064-1069.
Comer, S.D.; Burke, T.F.; Lewis, J.W.; Woods, J.H. Clocinnamox: a novel, systemically-active, irreversible opioid antagonist. J. Pharmacol. Exp. Ther., 1992, 262(3), 1051-1056.
[PMID: 1326622]
Nemoto, T.; Iihara, Y.; Hirayama, S.; Iwai, T.; Higashi, E.; Fujii, H.; Nagase, H. Naltrindole derivatives with fluorinated ethyl substituents on the 17-nitrogen as δ opioid receptor inverse agonists. Bioorg. Med. Chem. Lett., 2015, 25(15), 2927-2930.
[] [PMID: 26048798]
Hirayama, S.; Iwai, T.; Higashi, E.; Nakamura, M.; Iwamatsu, C.; Itoh, K.; Nemoto, T.; Tanabe, M.; Fujii, H. Discovery of δ opioid receptor full inverse agonists and their effects on restraint stress-induced cognitive impairment in mice. ACS Chem. Neurosci., 2019, 10(5), 2237-2242.
[] [PMID: 30913383]
Higashi, E.; Hirayama, S.; Nikaido, J.; Shibasaki, M.; Kono, T.; Honjo, A.; Ikeda, H.; Kamei, J.; Fujii, H. Development of novel δ opioid receptor inverse agonists without a basic nitrogen atom and their antitussive effects in mice. ACS Chem. Neurosci., 2019, 10(9), 3939-3945.
[] [PMID: 31397148]
Granier, S.; Manglik, A.; Kruse, A.C.; Kobilka, T.S.; Thian, F.S.; Weis, W.I.; Kobilka, B.K. Structure of the δ-opioid receptor bound to naltrindole. Nature, 2012, 485(7398), 400-404.
[] [PMID: 22596164]
Fenalti, G.; Giguere, P.M.; Katritch, V.; Huang, X-P.; Thompson, A.A.; Cherezov, V.; Roth, B.L.; Stevens, R.C. Molecular control of δ-opioid receptor signalling. Nature, 2014, 506(7487), 191-196.
[] [PMID: 24413399]
Portoghese, P.S.; Nagase, H. MaloneyHuss, K.E.; Lin, C.E.; Takemori, A.E. Role of spacer and address components in peptidomimetic δ opioid receptor antagonists related to naltrindole. J. Med. Chem., 1991, 34(5), 1715-1720.
[] [PMID: 1851846]
Takemori, A.E.; Sultana, M.; Nagase, H.; Portoghese, P.S. Agonist and antagonist activities of ligands derived from naltrexone and oxymorphone. Life Sci., 1992, 50(20), 1491-1495.
[] [PMID: 1315896]
Portoghese, P.S.; Sultana, M.; Nagase, H.; Takemori, A.E. A highly selective δ1-opioid receptor antagonist: 7-benzylidenenal-trexone. Eur. J. Pharmacol., 1992, 218(1), 195-196.
[] [PMID: 1327826]
Mitch, C.H.; Leander, J.D.; Mendelsohn, L.G.; Shaw, W.N.; Wong, D.T.; Cantrell, B.E.; Johnson, B.G.; Reel, J.K.; Snoddy, J.D.; Takemori, A.E.; Zimmerman, D.M. 3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine: opioid antagonist with potent anorectant activity. J. Med. Chem., 1993, 36, 2842-2850.
[] [PMID: 8410999]
Gackenheimer, S.L.; Suter, T.M.; Pintar, J.E.; Quimby, S.J.; Wheeler, W.J.; Mitch, C.H.; Gehlert, D.R.; Statnick, M.A. Localization of opioid receptor antagonist [3H]-LY255582 binding sites in mouse brain: comparison with the distribution of mu, delta and kappa binding sites. Neuropeptides, 2005, 39(6), 559-567.
[] [PMID: 16289278]
Filliol, D.; Ghozland, S.; Chluba, J.; Martin, M.; Matthes, H.W.D.; Simonin, F.; Befort, K.; Gavériaux-Ruff, C.; Dierich, A.; LeMeur, M.; Valverde, O.; Maldonado, R.; Kieffer, B.L. Mice deficient for δ- and μ-opioid receptors exhibit opposing alterations of emotional responses. Nat. Genet., 2000, 25(2), 195-200.
[] [PMID: 10835636]
Broom, D.C.; Jutkiewicz, E.M.; Folk, J.E.; Traynor, J.R.; Rice, K.C.; Woods, J.H. Nonpeptidic δ-opioid receptor agonists reduce immobility in the forced swim assay in rats. Neuropsychopharmacology, 2002, 26(6), 744-755.
[] [PMID: 12007745]
Pradhan, A.A.; Walwyn, W.; Nozaki, C.; Filliol, D.; Erbs, E.; Matifas, A.; Evans, C.; Kieffer, B.L. Ligand-directed trafficking of the δ-opioid receptor in vivo: two paths toward analgesic tolerance. J. Neurosci., 2010, 30(49), 16459-16468.
[] [PMID: 21147985]
Saitoh, A.; Yoshikawa, Y.; Onodera, K.; Kamei, J. Role of δ-opioid receptor subtypes in anxiety-related behaviors in the elevated plus-maze in rats. Psychopharmacology (Berl.), 2005, 182(3), 327-334.
[] [PMID: 16075288]
Schulteis, G.; Martinez, J.L., Jr ICI 174,864, a selective delta opioid antagonist, reverses the learning impairment produced by [leu]enkephalin. Psychopharmacology (Berl.), 1990, 100(1), 102-109.
[] [PMID: 2153306]
Ukai, M.; Takada, A.; Sasaki, Y.; Kameyama, T. Stimulation of δ1- and δ2-opioid receptors produces amnesia in mice. Eur. J. Pharmacol., 1997, 338(1), 1-6.
[] [PMID: 9407996]
Melo, I.; Drews, E.; Zimmer, A.; Bilkei-Gorzo, A. Enkephalin knockout male mice are resistant to chronic mild stress. Genes Brain Behav., 2014, 13(6), 550-558.
[] [PMID: 24804898]
Mizoguchi, K.; Yuzurihara, M.; Ishige, A.; Sasaki, H.; Chui, D.H.; Tabira, T. Chronic stress induces impairment of spatial working memory because of prefrontal dopaminergic dysfunction. J. Neurosci., 2000, 20(4), 1568-1574.
[] [PMID: 10662846]
Sarter, M.; Bodewitz, G.; Stephens, D.N. Attenuation of scopolamine-induced impairment of spontaneous alteration behaviour by antagonist but not inverse agonist and agonist β-carbolines. Psychopharmacology (Berl.), 1988, 94(4), 491-495.
[] [PMID: 2836875]
Kamei, J.; Iwamoto, Y.; Suzuki, T.; Misawa, M.; Nagase, H.; Kasuya, Y. Antitussive effects of naltrindole, a selective δ-opioid receptor antagonist, in mice and rats. Eur. J. Pharmacol., 1993, 249(2), 161-165.
[] [PMID: 8287897]
Kamei, J.; Iwamoto, Y.; Suzuki, T.; Misawa, M.; Nagase, H.; Kasuya, Y. Involvement of δ1-opioid receptor antagonism in the antitussive effect of δ-opioid receptor antagonists. Eur. J. Pharmacol., 1994, 251(2-3), 291-294.
[] [PMID: 8149982]
Kamei, J. δ-opioid receptor antagonists as a new concept for central acting antitussive drugs. Pulm. Pharmacol. Ther., 2002, 15(3), 235-240.
[] [PMID: 12099770]
Calderon, S.N.; Rothman, R.B.; Porreca, F.; Flippen-Anderson, J.L.; McNutt, R.W.; Xu, H.; Smith, L.E.; Bilsky, E.J.; Davis, P.; Rice, K.C. Probes for narcotic receptor mediated phenomena. 19. Synthesis of (+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-pipera-zinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC 80): a highly selective, nonpeptide delta opioid receptor agonist. J. Med. Chem., 1994, 37(14), 2125-2128.
[] [PMID: 8035418]
Szekeres, P.G.; Traynor, J.R. Delta opioid modulation of the binding of guanosine-5′-O-(3-[35S]thio)triphosphate to NG108-15 cell membranes: characterization of agonist and inverse agonist effects. J. Pharmacol. Exp. Ther., 1997, 283(3), 1276-1284.
[PMID: 9400003]

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