title: A review of the discovery, pharmacological characterization, and behavioral effects of the dopamine D2-like receptor antagonist eticlopride.
abstract: Eticlopride is a substituted benzamide analog with high affinity and selectivity for dopamine (DA) D2-like receptors that was initially developed as a potential antipsychotic agent. A great deal of research has utilized this drug to better understand central DA receptor function, the role of D2-like receptors in behavior, and the influence of blockade of these receptors on several preclinical animal models. This review highlights research utilizing this drug and compares it to typical and atypical antipsychotics used clinically. First, we describe structure-activity relationships as it relates to binding at DA receptors and the consequences on behavior. This is followed by a discussion of several imaging strategies including the use of eticlopride for in vivo, in vitro, and ex vivo examination of DA D2-like receptor densities and function. Finally, we discuss the use of eticlopride in several behavioral models predictive of antipsychotic activity, extrapyramidal side effects (EPS), and learning and memory. While eticlopride is not used clinically, it remains a viable research tool for understanding DA receptor function and behavior.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Martelle
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nader
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D012457:Salicylamides / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D012457:Salicylamides; C045989:eticlopride; D004298:Dopamine
references.citation: Mol Cell Biochem. 1983;53-54(1-2):129-52
references.pmid: 6137760
references.citation: Synapse. 2005 Dec 15;58(4):215-9
references.pmid: 16206180
references.citation: Proc Natl Acad Sci U S A. 1974 Apr;71(4):1113-7
references.pmid: 4151517
references.citation: Lancet. 1993 Nov 13;342(8881):1244-5
references.pmid: 7901566
references.citation: Physiol Behav. 1997 Apr;61(4):563-7
references.pmid: 9108576
references.citation: Annu Rev Neurosci. 1983;6:43-71
references.pmid: 6220666
references.citation: Prog Clin Biol Res. 1989;291:369-72
references.pmid: 2726875
references.citation: Trends Neurosci. 1991 Jan;14(1):21-7
references.pmid: 1709528
references.citation: J Pharm Sci. 1994 Mar;83(3):305-15
references.pmid: 8207673
references.citation: Pharm Res. 2002 Aug;19(8):1150-9
references.pmid: 12240941
references.citation: Eur J Pharmacol. 1978 Aug 15;50(4):459-61
references.pmid: 699970
references.citation: Science. 1953 Aug 7;118(3058):157-8
references.pmid: 13076224
references.citation: Med J Aust. 1994 May 2;160(9):591
references.pmid: 8018165
references.citation: Behav Pharmacol. 1994 Apr;5(2):141-152
references.pmid: 11224262
references.citation: Mol Pharmacol. 1994 Jan;45(1):51-60
references.pmid: 8302280
references.citation: Science. 1986 Dec 19;234(4783):1558-63
references.pmid: 2878495
references.citation: Behav Pharmacol. 1990;1(6):469-490
references.pmid: 11175433
references.citation: Nature. 1990 Sep 13;347(6289):146-51
references.pmid: 1975644
references.citation: Proc Natl Acad Sci U S A. 1972 Aug;69(8):2145-9
references.pmid: 4403305
references.citation: J Med Chem. 1985 Sep;28(9):1263-9
references.pmid: 4040977
references.citation: Med Res Rev. 1988 Oct-Dec;8(4):475-97
references.pmid: 2903950
references.citation: Acta Pharmacol Toxicol (Copenh). 1986 Jan;58(1):61-70
references.pmid: 2869639
references.citation: J Pharmacol Exp Ther. 1994 Aug;270(2):475-9
references.pmid: 8071839
references.citation: Psychopharmacol Commun. 1975;1(6):663-73
references.pmid: 1241457
references.citation: Arch Gen Psychiatry. 1993 Feb;50(2):85-94
references.pmid: 8427558
references.citation: Psychopharmacology (Berl). 1980;69(2):225-6
references.pmid: 6779316
references.citation: Pharmacol Rev. 1980 Sep;32(3):229-313
references.pmid: 6117090
references.citation: Neuroscience. 1991;45(2):359-71
references.pmid: 1762683
references.citation: J Med Chem. 1982 Nov;25(11):1280-6
references.pmid: 6128419
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1991;15(6):885-93
references.pmid: 1837159
references.citation: Acta Psychiatr Scand. 1992 Nov;86(5):391-8
references.pmid: 1485530
references.citation: Behav Pharmacol. 2000 Jun;11(3-4):223-33
references.pmid: 11103877
references.citation: Neurosci Lett. 1976 Dec;3(5-6):335-9
references.pmid: 19604908
references.citation: Psychopharmacology (Berl). 1988;94(1):1-7
references.pmid: 3126517
references.citation: Acta Pharm Suec. 1985;22(2):101-10
references.pmid: 4050456
references.citation: Pharmacol Biochem Behav. 1981 Feb;14(2):181-92
references.pmid: 6111088
references.citation: J Med Chem. 1986 Jan;29(1):61-9
references.pmid: 3941414
references.citation: C R Acad Sci III. 1990;311(13):501-8
references.pmid: 2129115
references.citation: Neuroscience. 1991;41(2-3):473-81
references.pmid: 1678501
references.citation: Acta Pharm Suec. 1979;16(4):239-46
references.pmid: 44421
references.citation: Pharmacol Biochem Behav. 1992 Jan;41(1):29-35
references.pmid: 1347175
references.citation: J Psychiatry Neurosci. 1995 Jul;20(4):287-96
references.pmid: 7647082
references.citation: J Exp Anal Behav. 1991 Sep;56(2):239-60
references.pmid: 1955815
references.citation: Chem Pharm Bull (Tokyo). 1992 Jul;40(7):1793-8
references.pmid: 1394695
references.citation: Neuropharmacology. 1986 Feb;25(2):187-97
references.pmid: 2939362
references.citation: Nature. 1976 Jun 24;261(5562):717-9
references.pmid: 945467
references.citation: Eur J Pharmacol. 1993 Jul 6;238(1):121-5
references.pmid: 8405075
references.citation: Arch Gen Psychiatry. 2006 Jun;63(6):679-85
references.pmid: 16754841
references.citation: Behav Pharmacol. 1990;1(4):355-363
references.pmid: 11175420
references.citation: Eur J Pharmacol. 1979 Jul 1;56(4):411-2
references.pmid: 477735
references.citation: Behav Neurosci. 2000 Jun;114(3):647-51
references.pmid: 10883814
references.citation: Nature. 1990 Sep 6;347(6288):72-6
references.pmid: 2144334
references.citation: Eur J Pharmacol. 1975 May;32(1):87-92
references.pmid: 1171020
references.citation: Neuropsychopharmacology. 1987 Dec;1(1):5-15
references.pmid: 2908095
references.citation: Neuroscience. 2000;96(3):451-74
references.pmid: 10717427
references.citation: Int Clin Psychopharmacol. 1989 Jan;4(1):61-70
references.pmid: 2531773
references.citation: Int J Rad Appl Instrum A. 1990;41(7):669-74
references.pmid: 2170298
references.citation: Int J Rad Appl Instrum B. 1990;17(4):347-56
references.pmid: 2143753
references.citation: Psychopharmacology (Berl). 1978 Apr 11;56(3):239-47
references.pmid: 26097
references.citation: Acta Pharm Suec. 1987;24(6):289-328
references.pmid: 2898864
references.citation: Brain Res. 1991 Nov 15;564(2):203-19
references.pmid: 1839781
references.citation: Neurosci Lett. 1986 May 6;66(1):85-90
references.pmid: 2940480
references.citation: J Neural Transm (Vienna). 1996;103(10):1163-75
references.pmid: 9013403
references.citation: Eur J Pharmacol. 1973 Oct;24(1):8-24
references.pmid: 4796448
references.citation: Eur J Pharmacol. 1994 Feb 21;253(1-2):167-9
references.pmid: 8013542
references.citation: J Histochem Cytochem. 1987 Aug;35(8):917-28
references.pmid: 2439585
references.citation: Science. 1975 Jun 13;188(4193):1084-9
references.pmid: 2976
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 1994 May;18(3):619-23
references.pmid: 8078994
references.citation: Proc Natl Acad Sci U S A. 1985 Jun;82(11):3863-7
references.pmid: 3873656
references.citation: Neurosci Lett. 1979 Jun;13(1):51-6
references.pmid: 572522
references.citation: Schizophr Bull. 1988;14(2):209-16
references.pmid: 3059468
references.citation: Eur J Pharmacol. 1993 Nov 16;249(3):R9-10
references.pmid: 8287911
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11271-5
references.pmid: 7972046
references.citation: Curr Pharm Des. 2003;9(8):673-96
references.pmid: 12570798
references.citation: Med Hypotheses. 1984 May;14(1):69-81
references.pmid: 6146915
references.citation: J Neurosci. 1982 Jul;2(7):895-906
references.pmid: 6124583
references.citation: Acta Pharmacol Toxicol (Copenh). 1963;20:140-4
references.pmid: 14060771
references.citation: Nature. 1988 Dec 22-29;336(6201):783-7
references.pmid: 2974511
references.citation: J Pharmacol Exp Ther. 1994 Jan;268(1):495-502
references.pmid: 8301592
references.citation: Eur J Pharmacol. 1978 Jun 1;49(3):295-9
references.pmid: 658143
references.citation: J Nucl Med. 1991 Aug;32(8):1593-600
references.pmid: 1831229
references.citation: Lancet. 1995 Sep 16;346(8977):743-9
references.pmid: 7658878
references.citation: Pharmacol Res. 1995 May;31(5):261-7
references.pmid: 7479522
references.citation: Adv Exp Med Biol. 1988;235:55-63
references.pmid: 2976254
references.citation: Synapse. 1987;1(2):133-52
references.pmid: 2905529
references.citation: Nature. 1991 Apr 18;350(6319):610-4
references.pmid: 1840645
references.citation: Eur J Clin Pharmacol. 1980 May;17(5):385-91
references.pmid: 7418717
references.citation: Trends Pharmacol Sci. 1992 Feb;13(2):61-9
references.pmid: 1561715
references.citation: Psychopharmacology (Berl). 1999 Nov;147(2):143-52
references.pmid: 10591881
references.citation: Drug Des Discov. 1993;9(3-4):333-50
references.pmid: 8400011
references.citation: Eur J Pharmacol. 1976 Jan;35(1):45-58
references.pmid: 3421
references.citation: Psychopharmacology (Berl). 1998 Nov;140(1):81-90
references.pmid: 9862406
references.citation: Psychopharmacol Bull. 1991;27(1):47-50
references.pmid: 1677773
references.citation: Pharmacol Toxicol. 1993 Dec;73(6):325-34
references.pmid: 8153056
references.citation: Neuropeptides. 2001 Oct-Dec;35(5-6):204-10
references.pmid: 12030803
references.citation: Eur J Pharmacol. 1993 Aug 3;239(1-3):269-70
references.pmid: 8223909
references.citation: Life Sci. 1979 Aug 6;25(6):479-85
references.pmid: 40086
references.citation: Psychopharmacology (Berl). 2000 Mar;148(4):355-60
references.pmid: 10928307
references.citation: Eur J Pharmacol. 1979 Jun 15;56(3):291-2
references.pmid: 477726
references.citation: Acta Psychiatr Scand. 1993 Feb;87(2):114-7
references.pmid: 8447237
references.citation: Eur J Pharmacol. 1985 May 8;111(2):191-9
references.pmid: 4018125
references.citation: J Med Chem. 1993 Jan 22;36(2):196-204
references.pmid: 8423592
references.citation: Eur J Pharmacol. 1986 Jan 21;120(2):217-26
references.pmid: 3948920
references.citation: Psychopharmacology (Berl). 1993;112(2-3):371-4
references.pmid: 7871044
references.citation: J Nucl Med. 2006 Feb;47(2):302-12
references.pmid: 16455637
references.citation: Proc Natl Acad Sci U S A. 1990 Sep;87(17):6723-7
references.pmid: 2168556
references.citation: Synapse. 1996 Jun;23(2):115-23
references.pmid: 8723716
references.citation: Proc Natl Acad Sci U S A. 1974 Jul;71(7):2915-8
references.pmid: 4527668
references.citation: Psychiatr Clin North Am. 1986 Mar;9(1):133-41
references.pmid: 2421270
references.citation: Int J Rad Appl Instrum B. 1991;18(8):871-81
references.pmid: 1839303
references.citation: Proc Natl Acad Sci U S A. 1989 Aug;86(16):6412-6
references.pmid: 2548214
references.citation: Eur J Pharmacol. 1979 Apr 15;55(2):137-42
references.pmid: 456412
references.citation: Eur J Pharmacol. 1984 Jul 20;102(3-4):459-74
references.pmid: 6149133
references.citation: Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):649-53
references.pmid: 7904756