, Volume 174, Issue 3, pp 301–319 | Cite as

Sigma receptors: biology and therapeutic potential

  • Xavier Guitart
  • Xavier Codony
  • Xavier Monroy


More than 20 years after the identification of the sigma receptors as a unique binding site in the brain and in the peripheral organs, several questions regarding this receptor are still open. Only one of the subtypes of the receptor has been cloned to date, but the endogenous ligand still remains unknown, and the possible association of the receptor with a conventional second messenger system is controversial. From the very beginning, the sigma receptors were associated with various central nervous system disorders such as schizophrenia or movement disorders. Today, after hundreds of papers dealing with the importance of sigma receptors in brain function, it is widely accepted that sigma receptors represent a new and different avenue in the possible pharmacological treatment of several brain-related disorders. In this review, what is known about the biology of the sigma receptor regarding its putative structure and its distribution in the central nervous system is summarized first. The role of sigma receptors regulating cellular functions and other neurotransmitter systems is also addressed, as well as a short overview of the possible endogenous ligands. Finally, although no specific sigma ligand has reached the market, different pharmacological approaches to the alleviation and treatment of several central nervous system disorders and deficits, including schizophrenia, pain, memory deficits, etc., are discussed, with an overview of different compounds and their potential therapeutic use.


Sigma receptors Schizophrenia Drug abuse Clinical potential Brain disorder 


  1. Akunne HC, Zoski KT, Whetzel SZ, Cordon JJ, Brandon RM, Roman F, Pugsley TA (2001) Neuropharmacological profile of a selective sigma ligand igmesine: a potential antidepressant. Neuropharmacology 41:138–149CrossRefGoogle Scholar
  2. Alonso G, Phan V-L, Guillemain I, Saunier M, Legrand A, Anoal M, Maurice T (2000) Immunocytochemical localization of the sigma1 receptor in the adult rat central nervous system. Neuroscience 97:155–170CrossRefPubMedGoogle Scholar
  3. Ault DT, Werling LL (1997) Differential modulation of NMDA-stimulated [3H]dopamine release from rat striatum by neuropeptide Y and sigma receptor ligands. Brain Res 760:210–217CrossRefPubMedGoogle Scholar
  4. Ault DT, Werling LL (1998) Neuropeptide Y-mediated enhancement of NMDA-stimulated [3H]dopamine release from rat prefrontal cortex is reversed by sigma1 receptor antagonists. Schizophr Res 31:27–36CrossRefPubMedGoogle Scholar
  5. Aydar E, Palmer CP, Klyachko VA, Jackson MB (2002) The sigma receptor as a ligand-regulated auxiliary potassium channel subunit. Neuron 34:399–410CrossRefPubMedGoogle Scholar
  6. Bartoszky GD, Bender HM, Hellman J, Schnorr C, Seyfred CA (1996) EMD 57445: a selective sigma ligand with the profile of an atypical neuroleptic. CNS Drug Rev 2:175–194Google Scholar
  7. Basile AS, Paul I, Mirchevich A, Kuijpers G, de Costa B (1992) Modulation of (+)-[3H]pentazocine binding to guinea pig cerebellum by divalent ions. Mol Pharmacol 42:882–889PubMedGoogle Scholar
  8. Beart PM, O’Shea RD, Manallack DT (1989) Regulation of sigma-receptors: high- and low-affinity agonist states GTP shifts and up-regulation by rimcazole and 13-Di(2-tolyl) guanidine. J Neurochem 53:779–788PubMedGoogle Scholar
  9. Bergeron R, Debonnel G (1997) Effects of low and high doses of selective sigma ligands: further evidence suggesting the existence of different subtypes of sigma receptors. Psychopharmacology 129:215–224CrossRefPubMedGoogle Scholar
  10. Bouchard P, Quirion R (1997) [3H]1,3-di(2-tolyl)guanidine and [3H](+)pentazocine binding sites in the rat brain: autoradiographic visualization of the putative sigma 1 and sigma 2 receptor subtypes. Neuroscience 76:467–477CrossRefPubMedGoogle Scholar
  11. Bouchard P, Maurice T, St-Pierre S, Privat A, Quirion R (1997)Neuropeptide Y and the calcitonin gene-related peptide attenuate learningimpairments induced by MK-801 via a sigma receptor-related mechanism. EurJ Neurosci 9:2142–2152Google Scholar
  12. Bowen WD (1994) Interaction of sigma receptors with signal transduction pathways and effects on second messengers. In: Itzhak Y (ed) Sigma receptors. Academic, San Diego, pp 139–170Google Scholar
  13. Bowen WD (2000) Sigma receptors: recent advances and new clinical potentials. Pharm Acta Helv 74:211–218CrossRefPubMedGoogle Scholar
  14. Bowen WD, Kirschner BN, Newman AH, Rice KC (1988) Sigma receptors negatively modulate agonist-stimulated phosphoinositide metabolism in rat brain. Eur J Pharmacol 177:111–118CrossRefGoogle Scholar
  15. Bowen WD, Walker JM, de Costa BR, Wu R, Tolentino PJ, Finn D, Rothman RB, Rice KC (1992) Characterization of the enantiomers of cis-N-[2-(34-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine (BD737 and BD738): novel compounds with high affinity selectivity and biological efficacy at sigma receptors. J Pharmacol Exp Ther 262:32–40PubMedGoogle Scholar
  16. Bowen WD, de Costa BR, Hellewell SB, Walker JM, Rice KC (1993) [3H](+)-Pentazocine: a potent and highly selective benzomorphan-based probe for sigma-1 receptors. Mol Neuropharmacol 3:117–126Google Scholar
  17. Bowen WD, Bertha CM, Vilner BJ, Rice KC (1995a) CB-64D and CB-184: ligands with high sigma-2 receptor affinity and subtype selectivity. Eur J Pharmacol 278:257–260CrossRefPubMedGoogle Scholar
  18. Bowen WD, Vilner BJ, Williams W, Bertha CM, Kuehne ME, Jacobson AE (1995b) Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate affinity. Eur J Pharmacol 279:R1–R3CrossRefPubMedGoogle Scholar
  19. Bowen WD, Vilner BJ, Bandarage UK, Kuehne ME (1996) Ibogaine and ibogamine modulate intracellular calcium levels via interaction with sigma-2 receptors. Soc Neurosci Abstr 22(7875):2006Google Scholar
  20. Bowlby MR (1993) Pregnenolone sulphate potentiation of N-methyl-d-aspartate receptor channels in hippocampal neurons. Mol Pharmacol 43:813–819PubMedGoogle Scholar
  21. Brady KT, Balster RL, May EL (1982) Stereoisomers of N-allylnormetazocine: phencyclidine-like behavioral effects in squirrel monkeys and rats. Science 215:178–180PubMedGoogle Scholar
  22. Chaki S, Tanaka M, Muramatsu M, Otomo S (1994) NE-100, a novel potent sigma ligand preferentially binds to sigma 1 binding sites in guinea pig brain. Eur J Pharmacol 251:R1–R2PubMedGoogle Scholar
  23. Chaki S, Okuyama S, Ogawa S, Tomisawa K (1998) Regulation of NMDA-induced [3H]dopamine release from rat hippocampal slices through sigma-1 binding sites. Neurochem Int 33:29–34PubMedGoogle Scholar
  24. Chien C-C, Pasternak GW (1993) Functional antagonism of morphine analgesia by (+)-pentazocine: evidence for an anti-opioid σ1 system. Eur J Pharmacol 250:R7–R8CrossRefPubMedGoogle Scholar
  25. Chien C-C, Pasternak GW (1994) Selective antagonism of opioid analgesia by a sigma system. J Pharmacol Exp Ther 271:1583–1590PubMedGoogle Scholar
  26. Chien C-C, Pasternak GW (1995) Sigma antagonists potentiate opioid analgesia in rats. Neurosci Lett 190:137–139CrossRefPubMedGoogle Scholar
  27. Church J, Fletcher EJ (1995) Blockade by sigma site ligands of high voltage-activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurons. Br J Pharmacol 116:2801–2810PubMedGoogle Scholar
  28. Clissold DB, Pontecorvo MJ, Jones BE, Abreu ME, Karbon EW, Erikson RH, Natalie KJ Jr, Borosky S, Hartman T, Mansbach RS, Balster RL, Ferkany JW, Enna SJ (1993) NPC 16377: a potent and selective σ-ligand. II. Behavioral and neuroprotective profile. J Pharmacol Exp Ther 265:876–886PubMedGoogle Scholar
  29. Connick JH, Hanlon G, Roberts J, France L, Fox PK, Nicholson CD (1992) Multiple sigma binding sites in guinea-pig and rat brain membranes: G-protein interactions. Br J Pharmacol 107:726–731PubMedGoogle Scholar
  30. de Costa BR, He X-S (1994) Structure–activity relationships and evolution of sigma receptor ligands (1976-present). In: Itzhak Y (ed) Sigma receptors. Academic, San Diego, pp 45–111Google Scholar
  31. Couture S, Debonnel G (1998) Modulation of the neuronal response to N-methyl-d-aspartate by selective sigma 2 ligands. Synapse 29:62–71CrossRefPubMedGoogle Scholar
  32. Craviso GL, Musacchio JM (1983) High affinity dextromethorphan binding sites in guinea pig. II. Competition experiments. Mol Pharmacol 23:629–640PubMedGoogle Scholar
  33. Crawford KW, Coop A, Bowen WD (2002) σ2 Receptors regulate changes in sphingolipid levels in breast tumor cells. Eur J Pharmacol 443:207–209CrossRefPubMedGoogle Scholar
  34. Cutts JM, de Costa BR, Bowen WD (1993) Sigma ligands have reduced ability to inhibit the muscarinic phosphoinositide response in cells deficient in sigma-1 receptors. In: Harris LS (ed) Problems of Drug Dependence 1992. Proceedings of the 54th annual scientific meeting, National Institute of Drug Abuse Research Monograph 132, US Government Printing Office, p 403Google Scholar
  35. Debonnel G (1993) Current hypotheses on sigma receptors and their physiological role: possible implications in psychiatry. J Psychiatry Neurosci 18:157–172PubMedGoogle Scholar
  36. Debonnel G, deMontigny C (1996) Modulation of NMDA and dopaminergic neurotransmission by sigma ligands: possible implications for the treatment of psychiatric disorders. Life Sci 58:721–734PubMedGoogle Scholar
  37. DeHaven-Hudkins DL, Fleissner LC (1992) Competitive interactions at [3H]-13-(2-tolyl)guanidine (DTG)-defined sigma recognition sites in guinea pig brain. Life Sci 50:PL65–PL70CrossRefPubMedGoogle Scholar
  38. DeHaven-Hudkins DL, Fleissner LC, Ford-Rice FY (1992) Characterization of the binding of [3H](+)-pentazocine to sigma recognition sites in guinea pig brain. Eur J Pharmacol 227:371–378CrossRefPubMedGoogle Scholar
  39. Derbez AE, Mode RM, Werling LL (2002) σ2-Receptor regulation of dopamine transporter via activation of protein kinase C. J Pharmacol Exp Ther 301:306–314CrossRefPubMedGoogle Scholar
  40. Dumont M, Lemaire S (1991) Interaction of 1,3-di(2-[5-3H]tolyl)guanidine with σ-2 binding sites in rat heart membrane preparations. Eur J Pharmacol 209:245–248CrossRefPubMedGoogle Scholar
  41. Earley B, Burke M, Leonard BE, Gouret CJ, Junien JL (1991) Evidence for an anti-amnesic effect of JO 1784 in the rat: a potent and selective ligand for the sigma receptor. Brain Res 546:282–286PubMedGoogle Scholar
  42. Ela C, Barg J, Vogel Z, Hasin Y, Eliam Y (1994) Sigma receptor ligands modulate contractility Ca++ influx and beating rate in cultured cardiac myocytes. J Pharmacol Exp Ther 269:1300–1309Google Scholar
  43. Ela C, Hasin Y, Eilam Y (1996) Apparent desensitization of a sigma receptor sub-population in neonatal rat cardiac myocytes by pre-treatment with sigma receptor ligands. Eur J Pharmacol 295:275–280CrossRefPubMedGoogle Scholar
  44. Ericson H, Ross SB (1992) Subchronic treatment of rats with remoxipride fails to modify σ binding sites in the brain. Eur J Pharmacol 226:157–161CrossRefPubMedGoogle Scholar
  45. Fitzgerald LW, Deutch AY, Gasic G, Heinemann SF, Nestler EJ (1995) Regulation of cortical and subcortical glutamate receptor subunit expression by antipsychotic drugs. J Neurosci 15:2453–2461PubMedGoogle Scholar
  46. Flood JF, Morley JE, Roberts E (1992) Memory-enhancing effects in male mice of pregnenolone and steroids metabolically derived from it. Proc Natl Acad Sci U S A 89:1567–1571PubMedGoogle Scholar
  47. Frieboes RM, Murck H, Wiedemann K, Holsboer F, Steiger A (1997) Open clinical trial of the sigma ligand panamesine in patients with schizophrenia. Psychopharmacology 132:82–88CrossRefPubMedGoogle Scholar
  48. Gebreselassie D, Bowen WD (2002) σ2 Receptors are components of sphingolipid/cholesterol-rich membrane rafts. Soc Neurosci Abstr 235.20Google Scholar
  49. Gewirtz GR, Gorman JM, Volavka J, Macaluso J, Gribkoff G, Taylor DP, Borison R (1994) BMY 14802, a sigma receptor ligand for the treatment of schizophrenia. Neuropsychopharmacology 10:37–40PubMedGoogle Scholar
  50. Ghelardini C, Galeotti N, Bartolini A (2000) Pharmacological identification of SM-21, the novel sigma(2) antagonist. Pharmacol Biochem Behav 67:659–662Google Scholar
  51. Gillgan PJ, Tam SW (1994) Sigma receptor ligands: potential drugs for the treatment of CNS disorders? Drug News Perspect 7:13–18Google Scholar
  52. Gonzalez-Alvear GM, Werling LL (1995) Sigma1 receptors in rat striatum regulate NMDA-stimulated [3H]dopamine release via a presynaptic mechanism. Eur J Pharmacol 294:713–719Google Scholar
  53. Gore AC (2001) Gonadotropin-releasing hormone neurons NMDA receptors and their regulation by steroid hormones across the reproductive life cycle. Brain Res Rev 37:235–248CrossRefPubMedGoogle Scholar
  54. Gronier B, Debonnel G (1999) Involvement of sigma receptors in the modulation of the glutamatergic/NMDA neurotransmission in the dopaminergic systems. Eur J Pharmacol 368:183–196PubMedGoogle Scholar
  55. Grunder G, Muller MJ, Andreas J, Heydari N, Wetzel H, Schlosser R, Schlegel S, Nickel O, Eissner D, Benkert O (1999) Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445: a putative atypical antipsychotic. Psychopharmacology 146:81–86CrossRefPubMedGoogle Scholar
  56. Guitart X, Farré AJ (1998) The effect of E-5842, a σ receptor ligand and potential atypical antipsychotic on Fos expression in rat forebrain. Eur J Pharmacol 363:127–130CrossRefPubMedGoogle Scholar
  57. Guitart X, Codony X, Ballarín M, Dordal A, Farré AJ (1998) E-5842: a new potent and preferential sigma ligand: preclinical pharmacological profile. CNS Drug Rev 4:201–224Google Scholar
  58. Guitart X, Méndez R, Ovalle S, Andreu F, Carceller A, Farré AJ, Zamanillo D (2000) Regulation of ionotropic glutamate receptor subunits in different rat brain areas by a preferential sigma1 receptor ligand and potential atypical antipsychotic. Neuropsychopharmacology 23:539–546CrossRefPubMedGoogle Scholar
  59. Gundlach AL, Largent BL, Snyder SH (1986) Autoradiographic localization of sigma receptor binding sites in guinea pig and rat central nervous system with (+)3H-3-(3-hydroxyphenyl)-N-(1-propyl)-piperidine. J Neurosci 6:642–647Google Scholar
  60. Haertzen CA (1970) Subjective effects of narcotic antagonists cyclazocine and nalorphine on the addiction research center inventory (ARCI). Psychopharmacologia 18:366–377PubMedGoogle Scholar
  61. Hanner M, Moebius FF, Weber F, Grabner M, Striessnig J, Glossmann (1995) Phenylalkylamine Ca2+ antagonist binding protein. Molecular cloning, tissue distribution and heterologous expression. J Biol Chem 271:7551–7557Google Scholar
  62. Hanner M, Moebius FF, Flandorfer A, Knaus HG, Striessnig J, Kempner E, Glossmann H (1996) Purification molecular cloning and expression of the mammalian sigma1-binding site. Proc Natl Acad Sci U S A 93:8072–8077CrossRefPubMedGoogle Scholar
  63. Hayashi T, Su T-P (2001) Regulating ankyrin dynamics: roles of sigma-1 receptors. Proc Natl Acad Sci U S A 98:491–496CrossRefPubMedGoogle Scholar
  64. Hayashi T, Kagaya A, Takebayashi M, Shimizu M, Uchitomi Y, Motohashi N, Yamawaki S (1995) Modulation by sigma ligands of intracellular free Ca++ mobilization by N-methyl-d-aspartate in primary culture of rat frontal cortical neurons. J Pharmacol Exp Ther 275:207–214PubMedGoogle Scholar
  65. Hayashi T, Maurice T, Su TP (2000) Ca (2+) signaling via sigma(1)-receptors: novel regulatory mechanism affecting intracellular Ca (2+)concentration. J Pharmacol Exp Ther 293:788–798PubMedGoogle Scholar
  66. Heading C (2001) Siramesine. Curr Opin Investig Drugs 2:266–270PubMedGoogle Scholar
  67. Hellewell SB, Bowen WD (1990) A sigma-like binding site in rat pheochromocytoma (PC12) cells: decreased affinity for (+)-benzomorphans and lower molecular weight suggest a different sigma receptor form from that in guinea pig brain. Brain Res 527:244–253PubMedGoogle Scholar
  68. Hellewell SB, Bruce A, Feinstein G, Orringer J, Williams W, Bowen WD (1994) Rat liver and kidney contain high densities of sigma-1 and sigma-2 receptors: characterization by ligand binding and photoaffinity labeling. Eur J Pharmacol Mol Pharmacol Sect 268:9–18CrossRefGoogle Scholar
  69. Hong W, Werling LL (2000) Evidence that the sigma(1) receptor is not directly coupled to G proteins. Eur J Pharmacol 408:117–125CrossRefPubMedGoogle Scholar
  70. Hong W, Werling LL (2001) Lack of effects by s ligands on neuropeptide Y-induced G-protein activation in rat hippocampus and cerebellum. Brain Res 901:208–218CrossRefPubMedGoogle Scholar
  71. Inoue A, Sugita S, Shoji H, Ichimoto H, Hide I, Nakata Y (2000) Repeated haloperidol treatment decreases σ1 receptor binding but does not affect its mRNA levels in the guinea pig or rat brain. Eur J Pharmacol 401:307–316CrossRefPubMedGoogle Scholar
  72. Ishiguro H, Ohtsuki T, Toru M, Itokawa M, Aoki J, Shibuya H, Kurumaji A, Okubo Y, Iwawaki A, Ota K, Shimizu H, Hamaguchi H, Arinami T (1998) Association between polymorphisms in the type 1 sigma receptor gene and schizophrenia. Neurosci Lett 257:45–48CrossRefPubMedGoogle Scholar
  73. Itzhak Y (1993) Repeated methamphetamine-treatment alters brain sigma receptors. Eur J Pharmacol 230:243–244CrossRefPubMedGoogle Scholar
  74. Itzhak Y (1994) Multiple sigma binding sites in the brain. In: Itzhak Y (ed) Sigma receptors. Academic, San Diego, pp 113–137Google Scholar
  75. Iwamoto ET (1981) Locomotor activity and antinociception after putative mu, kappa and sigma opioid receptor agonists in the rat: influence of dopaminergic agonists and antagonists. J Pharmacol Exp Ther 217:451–460PubMedGoogle Scholar
  76. Izenwasser S, Thompson-Montgomery D, Deben SE, Chowdhury IN, Werling LL (1998) Modulation of amphetamine-stimulated (transporter-mediated) dopamine release in vitro by σ2 receptor agonists and antagonists. Eur J Pharmacol 346:189–196CrossRefPubMedGoogle Scholar
  77. Jansen KLR, Faull RLM, Dragunow M, Leslie RA (1991) Autoradiographic distribution of sigma receptors in human neocortex hippocampus basal ganglia cerebellum pineal and pituitary glands. Brain Res 559:172–177CrossRefPubMedGoogle Scholar
  78. Jansen KL, Elliot M, Leslie RA (1992) Sigma receptors in rat brain and testes show similar reductions in response to chronic haloperidol. Eur J Pharmacol 214:281–283CrossRefPubMedGoogle Scholar
  79. Jonas EA, Kaczmarek LK (1996) Regulation of potassium channels by protein kinases. Curr Opin Neurobiol 6:318–323CrossRefPubMedGoogle Scholar
  80. Karasawa J, Yamamoto H, Yamamoto T, Sagi N, Horikomi K, Sora I (2002) MS-377, a selective sigma receptor ligand indirectly blocks the action of PCP in the N-methyl-d-aspartate receptor ion-channel complex in primary cultured rat neuronal cells. Life Sci 70:1631–1642CrossRefPubMedGoogle Scholar
  81. Kekuda R, Prasad PD, Fei YJ, Leibach FH, Ganapathy V (1996) Cloning and functional expression of the human type 1 sigma receptor (hSigmaR 1). Biochem Biophys Res Commun 229:553–558CrossRefPubMedGoogle Scholar
  82. King MA, Pan Y-X, Mei J, Chang A, Xu J, Pasternak GW (1997) Enhanced kappa opioid analgesia by antisense targeting the σ1 receptor. Eur J Pharmacol 331:R5–R7CrossRefPubMedGoogle Scholar
  83. Klein MD, Musacchio JM (1989) High affinity dextromethorphan binding sites in guinea pig brain. Effect of sigma ligands and other agents. J Pharmacol Exp Ther 251:207–215PubMedGoogle Scholar
  84. Klein MD, Musacchio JM (1994) Effects of cytochrome P450 ligands on the binding of [3H]dextrometorphan and sigma ligands to guinea-pig brain. In: Itzhak Y (ed) Sigma receptors. Academic, San Diego, pp 243–262Google Scholar
  85. Klette KL, DeCoster MA, Moreton JE, Tortella FC (1995) Role of calcium in sigma-mediated neuroprotection in rat primary cortical neurons. Brain Res 704:31–41CrossRefPubMedGoogle Scholar
  86. Klette KL, Lin Y, Clapp LE, DeCoster MA, Moreton JE, Tortella FC (1997) Neuroprotective sigma ligands attenuate NMDA and trans-ACPD-induced calcium signaling in rat primary neurons. Brain Res 756:231–240PubMedGoogle Scholar
  87. Koe BK, Burkhart CA, Lebel LA (1989) (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)-piperidine binding to σ receptors in mouse brain in vivo. Eur J Pharmacol 161:263–266CrossRefPubMedGoogle Scholar
  88. Lambert JJ, Harney SC, Belelli D, Peters JA (2001) Neurosteroid modulation of recombinant and synaptic GABAA receptors. Int Rev Neurobiol 46:177–205PubMedGoogle Scholar
  89. Langa F, Codony X, Tovar V, Lavado A, Gimenez E, Cozar P, Cantero M, Dordal A, Hernández E, Pérez R, Monroy X, Zamanillo D, Guitart X, Montoliu L (2003) Generation and phenotypic analysis of sigma receptor type I (σ1) knockout mice. Eur J Neurosci 18:2188–2196CrossRefPubMedGoogle Scholar
  90. Largent BL, Gundlach AL, Snyder SH (1986) Pharmacological and autoradiographic discrimination of sigma and phencyclidine receptor binding sites in brain with (+)-[3H]SKF 10,047 (+)-[3H]-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine and [3H]-1-[1-(2-thienyl)cyclohexyl]-piperidine. J Pharmacol Exp Ther 238:739–748PubMedGoogle Scholar
  91. Leitner ML, Hohmann AG, Patrick SL, Walker JM (1994) Regional variation in the ratio of sigma 1 to sigma 2 binding in rat brain. Eur J Pharmacol 259:65–69CrossRefPubMedGoogle Scholar
  92. Lupardus PJ, Wilke RA, Aydar E, Palmer CP, Chen Y, Ruoho AE, Jackson MB (2000) Membrane-delimited coupling between sigma receptors and K+ channels in rat neurohypophysial terminals requires neither G-protein nor ATP. J Physiol 526:527–539PubMedGoogle Scholar
  93. Martin WR, Eades CE, Thompson JA, Huppler RE (1976) The effects of morphine and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther 197:517–532PubMedGoogle Scholar
  94. Maruo J, Yoshida A, Shimohira I, Matsuno K, Mita S, Ueda H (2000) Binding of [35S]GTPgammaS stimulated by (+)-pentazocine sigma receptor agonist is abundant in the guinea pig spleen. Life Sci 67:599–603CrossRefPubMedGoogle Scholar
  95. Matsumoto RR, Mack AL (2001) (±)-SM 21 attenuates the convulsive and locomotor stimulatory effects of cocaine in mice. Eur J Pharmacol 417:R1–R2CrossRefPubMedGoogle Scholar
  96. Matsumoto RR, Pouw B (2000) Correlation between neuroleptic binding to sigma(1) and sigma(2) receptors and acute dystonic reactions. Eur J Pharmacol 401:155–160CrossRefPubMedGoogle Scholar
  97. Matsumoto RR, Hemstreet MK, Lai NL, Thurkauf A, de Costa BR, Rice KC, Hellewell SB, Bowen WB, Walker JM (1990) Drug specificity of pharmacological dystonia. Pharmacol Biochem Behav 36:151–155CrossRefPubMedGoogle Scholar
  98. Matsumoto RR, Bowen WD, Tom MA, Vo VN, Truong DD, de Costa BR (1995) Characterization of two novel σ receptor ligands: antidystonic effects in rats suggests s receptor antagonism. Eur J Pharmacol 365:35–38Google Scholar
  99. Matsumoto RR, McCraken KA, Friedman MJ, Pouw B, de Costa BR, Bowen WD (2001) Conformationally restricted analogs of BD1008 and an antisense oligodeoxynucleotide targeting sigma 1 receptors produce anti-cocaine effects in mice. Eur J Pharmacol 419:163–174CrossRefPubMedGoogle Scholar
  100. Matsumoto RR, McCracken KA, Pouw B, Zhang Y, Bowen WD (2002) Involvement of sigma receptors in the behavioral effects of cocaine: evidence from novel ligands and antisense oligodeoxynucleotides. Neuropharmacology 42:1043–1055CrossRefPubMedGoogle Scholar
  101. Matsumoto RR, Liu Y, Lerner M, Howard EW, Brackett DJ (2003) Sigma receptors: potential medications development target for anti-cocaine agents. Eur J Pharmacol 469:1–12CrossRefPubMedGoogle Scholar
  102. Matsuno K, Matsunaga K, Senda T, Mita S (1993) Increase in extracellular acetylcholine level by sigma ligands in rat frontal cortex. J Pharmacol Exp Ther 265:851–859PubMedGoogle Scholar
  103. Matsuno K, Senda T, Matsunaga K, Mita S (1994) Ameliorating effects of sigma receptor ligands on the impairment of passive avoidance tasks in mice: involvement in the central acetylcholinergic system. Eur J Pharmacol 261:43–51CrossRefPubMedGoogle Scholar
  104. Matsuno K, Senda T, Kobayashi T, Mita S (1995) Involvement of sigma 1 receptor in (+)-N-allylnormetazocine-stimulated hippocampal cholinergic functions in rats. Brain Res 690:200–206CrossRefPubMedGoogle Scholar
  105. Matsuno K, Kobayashi T, Tanaka MK, Mita S (1996a) Sigma 1 receptor subtype is involved in the relief of behavioral despair in the mouse forced swimming test. Eur J Pharmacol 286:213–217Google Scholar
  106. Matsuno K, Nakazawa M, Okamoto K, Kawashima Y, Mita S (1996b) Binding properties of SA4503: a novel and selective sigma 1 receptor agonist. Eur J Pharmacol 306:271–279CrossRefPubMedGoogle Scholar
  107. Matsuno K, Senda T, Kobayashi T, Okamoto K, Nakata K, Mita S (1997) SA4503: a novel cognitive enhancer with sigma1 receptor agonistic properties. Behav Brain Res 83:221–224CrossRefPubMedGoogle Scholar
  108. Maurice T, Lockhart BP (1997) Neuroprotective and anti-amnesic potentials of sigma receptor ligands. Prog Neuropsychopharmacol Biol Psychiatry 21:69–102CrossRefPubMedGoogle Scholar
  109. Maurice T, Su TP, Parish DW, Nabeshima T, Privat A (1994) PRE-084: a sigma selective PCP derivative attenuates MK-801-induced impairment of learning in mice. Pharmacol Biochem Behav 49:859–869CrossRefPubMedGoogle Scholar
  110. Maurice T, Roman FJ, Privat A (1996) Modulation by neurosteroids of the in vivo (+)-[3H]SKF 10,047 binding to sigma1 receptors in the mouse forebrain. J Neurosci Res 46:734–743CrossRefPubMedGoogle Scholar
  111. Maurice T, Junien JL, Privat A (1997) Dehydroepiandrosterone sulphate attenuates dizocilpine-induced learning impairment in mice via σ1-receptors. Behav Brain Res 83:159–164Google Scholar
  112. Maurice T, Su TP, Privat A (1998) Sigma1 (σ1) receptor agonists and neurosteroids attenuate β25–35-amyloid peptide-induced amnesia in mice through a common mechanism. Neuroscience 83:413–428CrossRefPubMedGoogle Scholar
  113. Maurice T, Phan VL, Urani A, Kamei H, Noda Y, Nameshima T (1999) Neuroactive steroids as endogenous effectors for the sigma1 (σ1) receptor: pharmacological evidence and therapeutic opportunities. Jpn J Pharmacol 81:125–155Google Scholar
  114. Maurice T, Urani A, Phan V-L, Romieu P (2001) The interaction between neuroactive steroids and the σ1 receptor function: behavioral consequences and therapeutic opportunities. Brain Res Rev 37:116–132PubMedGoogle Scholar
  115. Maurice T, Martin-Fardon R, Romieu P, Matsumoto RR (2002) Sigma1(σ1) receptor antagonists represent a new strategy against cocaine addiction and toxicity. Neurosci Biobehav Rev 26:499–527CrossRefPubMedGoogle Scholar
  116. McCann DJ, Su TP (1990) Haloperidol-sensitive (+)[3H]SKF 10,047 binding sites (sigma sites) exhibit a unique distribution in rat brain subcellular fractions. Eur J Pharmacol 188:211–218CrossRefPubMedGoogle Scholar
  117. McCann DJ, Su T-P (1991) Solubilization and characterization of haloperidol-sensitive (+)-[3H]SKF 10,047 binding sites (sigma sites) from rat liver membranes. J Pharmacol Exp Ther 257:547–554PubMedGoogle Scholar
  118. McCann DJ, Weissman AD, Su TP (1994) Sigma-1 and sigma-2 sites in rat brain: comparison of regional ontogenic and subcellular patterns. Synapse 17:182–189PubMedGoogle Scholar
  119. McCraken KA, Bowen WD, Matsumoto RR (1999) Novel σ receptor ligands attenuate the locomotor stimulatory effects of cocaine. Eur J Pharmacol 365:35–38CrossRefPubMedGoogle Scholar
  120. McLean S, Weber E (1988) Autoradiographic visualization of haloperidol-sensitive sigma receptors in guinea-pig brain. Neuroscience 25:259–269PubMedGoogle Scholar
  121. Mei J, Pasternak GW (2001) Molecular cloning and pharmacological characterization of the rat sigma1 receptor. Biochem Pharmacol 62:349–355CrossRefPubMedGoogle Scholar
  122. Mei J, Pasternak GW (2002) σ1 Receptor modulation of opioid analgesia in the mouse. J Pharmacol Exp Ther 300:1070–1074CrossRefPubMedGoogle Scholar
  123. Mendelsohn LG, Kalra V, Johnson BG, Kerchner GA (1985) Sigma opioid receptor: characterization and co-identity with the phencyclidine receptor. J Pharmacol Exp Ther 233:597–602PubMedGoogle Scholar
  124. Menkel M, Terry P, Pontecorvo M, Katz JL, Witkin JM (1991) Selective sigma ligands block stimulant effects of cocaine. Eur J Pharmacol 201:251–252CrossRefPubMedGoogle Scholar
  125. Meyer C, Schmieding K, Falkenstein E, Wehling M (1998) Are high-affinity progesterone binding sites(s) from porcine liver microsomes members of the σ receptor family? Eur J Pharmacol 347:293–299CrossRefPubMedGoogle Scholar
  126. Moebius FF, Striessnig J, Glossmann H (1997a) The mysteries of sigma receptors: new family members reveal a role in cholesterol synthesis. Trends Pharmacol Sci 18:67–70CrossRefPubMedGoogle Scholar
  127. Moebius FF, Reiter RJ, Hanner M, Glossmann H (1997b) High affinity of sigma 1-binding sites for sterol isomerization inhibitors: evidence for a pharmacological relationship with the yeast sterol C8–C7 isomerase. Br J Pharmacol 121:1–6PubMedGoogle Scholar
  128. Moltzen EK, Perregaard J, Meier E (1995) Sigma ligands with subnanomolar affinity and preference for the sigma 2 binding site. 2. Spiro-joined benzofuran, isobenzofuran, and benzopyran piperidines. J Med Chem 38:2009–2017PubMedGoogle Scholar
  129. Monnet FP, Debonnel G, Junien JL, deMontigny C (1990) N-methyl-d-aspartate-induced neuronal activity is selectively modulated by sigma receptors. Eur J Pharmacol 179:441–445CrossRefPubMedGoogle Scholar
  130. Monnet FP, Blier P, Debonnel G, de Montigny C (1992a) Modulation by sigma ligands of N-methyl-d-aspartate-induced [3H]noradrenaline release. Naunyn Schmiedebergs Arch Pharmacol 346:32–39PubMedGoogle Scholar
  131. Monnet FP, Debonnel G, de Montigny C (1992b) In vivo electrophysiological evidence for a selective modulation of N-methyl-d-aspartate-induced neuronal activation in rat CA3 dorsal hippocampus by sigma ligands. J Pharmacol Exp Ther 261:123–130PubMedGoogle Scholar
  132. Monnet FP, Debonnel G, Fournier A, de Montigny C (1992c) Neuropeptide Y potentiates selectively the N-methyl-d-aspartate response in the CA3 dorsal hippocampus. II. Involvement of a subtype of sigma receptor. J Pharmacol Exp Ther 263:1219–1225PubMedGoogle Scholar
  133. Monnet FP, Fournier A, Debonnel G, de Montigny C (1992d) Neuropeptide Y potentiates selectively the N-methyl-d-aspartate response in the CA3 dorsal hippocampus. I. Involvement of an atypical neuropeptide Y receptor. J Pharmacol Exp Ther 263:1212–1218PubMedGoogle Scholar
  134. Monnet FP, Debonnel G, Bergeron R, Gronier B, de Montigny C (1994) The effects of sigma ligands and of neuropeptide Y on N-methyl-d-aspartate-induced neuronal activation of CA3 dorsal hippocampus neurones are differentially affected by pertussis toxin. Br J Pharmacol 112:709–715PubMedGoogle Scholar
  135. Monroy X, Romero G, Pérez MP, Farré AJ, Guitart X (2001) Decrease of adenylyl cyclase activity and expression by a sigma1 receptor ligand and putative atypical antipsychotic. Neuroreport 12:1989–1992CrossRefPubMedGoogle Scholar
  136. Morin-Surun MP, Collin T, Denavit-Saubié M, Baulieu E-E, Monnet FP (1999) Intracellular σ1 receptor modulates phospholipase C and protein kinase C activities in the brainstem. Proc Natl Acad Sci U S A 96:8196–8199CrossRefPubMedGoogle Scholar
  137. Morio Y, Tanimoto H, Yakushiji T, Morimoto Y (1994) Characterization of the currents induced by sigma ligands in NCB20 neuroblastoma cells. Brain Res 637:190–196CrossRefPubMedGoogle Scholar
  138. Nestler EJ (2001) Molecular neurobiology of addiction. Am J Addict 10:201–217CrossRefPubMedGoogle Scholar
  139. Novakova M (1998) Sigma receptors: with special reference to cardiac muscle. Exp Clin Cardiol 3:113–120Google Scholar
  140. Novakova M, Ela C, Barg J, Vogel Z, Hasin Y, Eilam Y (1995) Inotropic action of sigma receptor ligands in isolated cardiac myocytes from adult rats. Eur J Pharmacol 286:19–30CrossRefPubMedGoogle Scholar
  141. Novakova M, Ela C, Bowen WD, Hasin Y, Eilam Y (1998) Highly selective sigma receptor ligands elevate inositol 1,4,5-trisphosphate production in rat cardiac myocytes. Eur J Pharmacol 353:315–327Google Scholar
  142. Nuwayhid SJ, Werling LL (2003) σ1-Receptor agonist-mediated regulation of N-methyl-d-aspartate-stimulated [3H]dopamine release is dependent upon protein kinase C. J Pharmacol Exp Ther 304:364–369CrossRefPubMedGoogle Scholar
  143. Ohmori O, Shinkai T, Suzuki T, Okano C, Kojima H, Terao T, Nakamura J (2000) Polymorphisms of the sigma(1) receptor gene in schizophrenia: an association study. Am J Med Genet 96:118–122CrossRefPubMedGoogle Scholar
  144. Ohno M, Watanabe S (1995) Intrahippocampal administration of (+)-SKF 10,047: a sigma ligand reverses MK-801-induced impairment of working memory in rats. Brain Res 684:237–242CrossRefPubMedGoogle Scholar
  145. Okumura K, Ujike H, Akiyama K, Kuroda S (1996) BMY-14802 reversed the sigma receptor agonist-induced neck dystonia in rats. J Neural Transm 103:1153–1161PubMedGoogle Scholar
  146. Okuyama S, Imagawa Y, Ogawa S, Araki H, Ajima A, Tanaka M, Muramatsu M, Nakazato A, Yamaguchi K, Yoshida M, Otomo S (1993) NE-100, a novel sigma receptor ligand: in vivo tests. Life Sci 53:285–290Google Scholar
  147. Okuyama S, Imagawa Y, Sakagawa T, Nakazato A, Yamaguchi K, Katoh M, Yamada S, Araki H, Otomo S (1994) NE-100, a novel sigma receptor ligand: effect on phencyclidine-induced behaviors in rats dogs and monkeys. Life Sci 55:PL133–PL138PubMedGoogle Scholar
  148. Okuyama S, Chaki S, Yae T, Nakazato A, Muramatsu M (1995a) Autoradiographic characterization of binding sites for [3H]NE-100 in guinea pig brain. Life Sci 57:PL333–PL337PubMedGoogle Scholar
  149. Okuyama S, Ogawa S, Nakazato A, Tomizawa K (1995b) Effect of NE-100, a novel sigma receptor ligand on phencyclidine-induced delayed cognitive dysfunction in rats. Neurosci Lett 189:60–62CrossRefPubMedGoogle Scholar
  150. Oshiro Y, Sakurai Y, Sato S, Kurahashi N, Tanaka T, Kikuchi T, Tottori K, Uwahodo Y, Miwa T, Nishi T (2000) 3,4-Dihydro-2(1H))-quinolinone as a novel antidepressant drug: synthesis and pharmacology of 1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-3,4-dihydro-5-methoxy-2(1H)-quinolinone and its derivatives. J Med Chem 43:177–189CrossRefPubMedGoogle Scholar
  151. Pan YX, Mei JF, Xu J, Wan BL, Zuckerman A, Pasternak GW (1998) Cloning and characterization of a σ1 receptor. J Neurochem 70:2279–2285PubMedGoogle Scholar
  152. Pascaud XB, Chovet M, Roze C, Junien JL (1993) Neuropeptide Y and sigma receptor agonists act through a common pathway to stimulate duodenal alkaline secretion in rats. Eur J Pharmacol 231:389–394CrossRefPubMedGoogle Scholar
  153. Paul IA, Basile AS, Rojas E, Youdim MB, De Costa B, Skolnick P, Pollard HB, Kuijpers GA (1993) Sigma receptors modulate nicotinic receptor function in adrenal chromaffin cells. FASEB J 7:1171–1178PubMedGoogle Scholar
  154. Phan VL, Su TP, Privat A, Maurice T (1999) Modulation of steroidal levels by adrenalectomy/castration and inhibition of neurosteroid synthesis enzymes affect sigma1 receptor-mediated behaviour in mice. Eur J Neurosci 11:2385–2396PubMedGoogle Scholar
  155. Poncelet M, Santucci V, Paul R, Gueudet C, Lavastre S, Guitard J, Steinberg R, Terranova JP, Breliere JC, Soubrie P, Le Fur G (1993) Neuropharmacological profile of a novel and selective ligand of the sigma site: SR 31742A. Neuropharmacology 32:605–615CrossRefPubMedGoogle Scholar
  156. Prasad PD, Li HW, Fei YJ, Ganapathy ME, Fujita T, Plumley LH, Yang-Feng TL, Leibach FH, Ganapathy V (1998) Exon–intron structure analysis of promoter region and chromosomal localization of the human type 1 sigma receptor gene. J Neurochem 70:443–451PubMedGoogle Scholar
  157. Quirion R, Bowen WD, Itzhak Y, Junien JL, Musacchio JM, Rothman RB, Su T-P, Tam SW, Taylor DP (1992) A proposal for the classification of sigma binding sites. Trends Pharmacol Sci 13:85–86PubMedGoogle Scholar
  158. Ritz MC, George FR (1993) Cocaine-induced seizures and lethality appear to be associated with distinct central nervous system binding sites. J Pharmacol Exp Ther 264:1333–1343PubMedGoogle Scholar
  159. Roman F, Pascaud X, Duffy O, Vauche D, Martin B, Junien JL (1989a) Neuropeptide Y and peptide YY interact with rat brain sigma and PCP binding sites. Eur J Pharmacol 174:301–302CrossRefPubMedGoogle Scholar
  160. Roman F, Pascaud X, Chomette G, Bueno L, Junien JL (1989b) Autoradiographic localization of sigma opioid receptors in the gastrointestinal tract of the guinea pig. Gastroenterology 97:76–82PubMedGoogle Scholar
  161. Roman FJ, Pascaud X, Martin B, Vauche D, Junien JL (1990) JO 1784: a potent and selective ligand for rat and mouse brain σ-sites. Eur J Pharmacol 42:439–440Google Scholar
  162. Romero G, Pérez MP, Carceller A, Monroy X, Farré AJ, Guitart X (2000) Changes in phosphoinositide signalling activity and levels of the alpha subunit of Gq/11 protein in rat brain induced by E-5842, a sigma1 receptor ligand and potential atypical antipsychotic. Neurosci Lett 290:189–192CrossRefPubMedGoogle Scholar
  163. Romieu P, MartinFardon R, Maurice T (2000) Involvement of the sigma 1 receptor in the cocaine-induced conditioned place preference. Neuroreport 11:2885–2888PubMedGoogle Scholar
  164. Ross SB (1991) Heterogeneous binding of σ radioligands in the rat brain and liver: possible relationship to subforms of cytochrome P450. Pharmacol Toxicol 68:293–301PubMedGoogle Scholar
  165. Rothman RB, Reid A, Mahboubi A, Kim CH, De Costa BR, Jacobson AE, Rice KC (1991) Labeling by [3H]13-di(2-tolyl)guanidine of two high affinity binding sites in guinea pig brain: evidence for allosteric regulation by calcium channel antagonists and pseudoallosteric modulation by sigma ligands. Mol Pharmacol 39:222–232PubMedGoogle Scholar
  166. Ryan-Moro J, Chien CC, Standifer KM, Pasternak GW (1996) Sigma binding in a human neuroblastoma cell line. Neurochem Res 21:1309–1314PubMedGoogle Scholar
  167. Samovilova NN, Vinogradov VA (1992) Subcellular distribution of (+)-[3H]SKF 10047 binding sites in rat liver. Eur J Pharmacol Mol Pharmacol 225:69–74CrossRefGoogle Scholar
  168. Samovilova NN, Nagornaya LV, Vinogradov VA (1988) (+)-[3H]SKF 10,047 binding sites in rat liver. Eur J Pharmacol 147:259–264CrossRefPubMedGoogle Scholar
  169. Sanchez C, Papp M (2000) The selective sigma(2) ligand Lu 28-179 has an antidepressant-like profile in the rat chronic mild stress model of depression. Behav Pharmacol 11:117–124PubMedGoogle Scholar
  170. Sanchez C, Arnt J, Costall B, Kelly ME, Meier E, Naylor RJ, Perregaard J (1997) The selective sigma2-ligand Lu 28-179 has potent anxiolytic-like effects in rodents. J Pharmacol Exp Ther 283:1323–1332PubMedGoogle Scholar
  171. Schmidt A, Lebel L, Koe BK, Seeger T, Heym J (1989) Sertraline potently displaces (+)-[3H]3-PPP binding to sigma sites in rat brain. Eur J Pharmacol 165:335–336CrossRefPubMedGoogle Scholar
  172. Senda T, Matsuno K, Kobayashi T, Nakazawa M, Nakata K, Mita S (1998a) Ameliorative effect of SA4503, a novel cognitive enhancer on the basal forebrain lesion-induced impairment of the spatial learning performance in rats. Pharmacol Biochem Behav 59:129–134CrossRefPubMedGoogle Scholar
  173. Senda T, Mita S, Kaneda K, Kikuchi M, Akaike A (1998b) Effect of SA4503, a novel sigma1 receptor agonist against glutamate neurotoxicity in cultured rat retinal neurons. Eur J Pharmacol 42:105–111CrossRefGoogle Scholar
  174. Seth P, Fei YJ, Huang W, Leibach FH, Ganapathy V (1998) Cloning and functional characterization of a sigma receptor from rat brain. J Neurochem 70:922–931PubMedGoogle Scholar
  175. Sharkey J, Glen KA, Wolfe S, Kuhar MJ (1988) Cocaine binding at sigma receptors. Eur J Pharmacol 149:171–174CrossRefPubMedGoogle Scholar
  176. Soriani O, Foll FL, Roman F, Monnet FP, Vaudry H, Cazin L (1999) A-current down-modulated by sigma receptor in frog pituitary melanotrope cells through a G protein-dependent pathway. J Pharmacol Exp Ther 289:321–328PubMedGoogle Scholar
  177. Su TP (1993) Delineating biochemical and functional properties of sigma receptors: emerging concepts. Crit Rev Neurobiol 7:187–203PubMedGoogle Scholar
  178. Su T-P, Junien JL (1994) Sigma receptors in the central nervous system and the periphery. In: Itzhak Y (ed) Sigma receptors. Academic, San Diego, pp 21–44Google Scholar
  179. Su TP, Hayashi T (2001) Cocaine affects the dynamics of cytoskeletal proteins via sigma(1) receptors. Trends Pharmacol Sci 22:456–458CrossRefPubMedGoogle Scholar
  180. Su TP, Hayashi T (2003) Understanding the molecular mechanism of sigma-1 receptors: towards a hypothesis that sigma-1 receptors are intracellular amplifiers for signal transduction. Curr Med Chem 10:2073–2080PubMedGoogle Scholar
  181. Su T-P, London ED, Jaffe JH (1988) Steroid binding at sigma receptor suggests a link between endocrine nervous and immune systems. Science 240:219–221PubMedGoogle Scholar
  182. Su TP, Wu XZ, Cone EJ, Shukla K, Gund TM, Dodge AL, Parish DW (1991) Sigma compounds derived from phencyclidine: identification of PRE-084, a new selective sigma ligand. J Pharmacol Exp Ther 259:543–550PubMedGoogle Scholar
  183. Takahashi S, Sonehara K, Takagi K, Miwa T, Horikomi K, Mita N, Nagase H, Iizuka K, Sakai K (1999) Pharmacological profile of MS-377, a novel selective antipsychotic agent with selective affinity for sigma receptors. Psychopharmacology 145:295–302PubMedGoogle Scholar
  184. Takahashi S, Miwa T, Horikomi K (2000) Involvement of sigma 1 receptors in methamphetamine-induced behavioural sensitization in rats. Neurosci Lett 289:21–24PubMedGoogle Scholar
  185. Takebayashi M, Hayashi T, Su TP (2002) Nerve growth factor-induced neurite sprouting in PC12 cells involves sigma-1 receptors: implications for antidepressants. J Pharmacol Exp Ther 303:1227–1237CrossRefPubMedGoogle Scholar
  186. Tam SW, Mitchell KN (1991) Neuropeptide Y and peptide YY do not bind to brain sigma and phencyclidine binding sites. Eur J Pharmacol 193:121–122CrossRefPubMedGoogle Scholar
  187. Tam SW, Steinfels GF, Gilligan PJ, Schimdt WK, Cook L (1992) DuP 724 [1-(cyclopropylmethyl)-4-(2′(4″-fluorophenyl)-2′-oxoethyl)-piperidine HBr]: a sigma- and 5-hydroxytryptamine2 receptor antagonist; receptor-binding electrophysiological and neuropharmacological profiles. J Pharmacol Exp Ther 263:1167–1174PubMedGoogle Scholar
  188. Tascedda F, Lovati E, Blom JMC, Muzzioli P, Brunello N, Racagni G, Riva MA (1999) Regulation of ionotropic glutamate receptors in the rat brain in response to the atypical antipsychotic seroquel (quetiapine fumarate). Neuropsychopharmacology 21:211–217CrossRefPubMedGoogle Scholar
  189. Taylor DP, Dekleva J (1987) The potential antipsychotic BMY 14802 selectively binds to sigma sites. Fed Proc 46:1304Google Scholar
  190. Taylor DP, Eison MS, Moon SL, Schlemmer RF Jr, Shukla UA, VanderMaelen CP, Yocca FD, Gallant DJ, Behling SH, Boissard CG, Braselton JP, Davis HH Jr, Duquette MN, Lamy RC, Libera JM, Ryan E, Wright RN (1993) A role for σ binding in the antipsychotic profile of BMY 14802? In: Souza EB, Clouet D, London E (eds) Sigma PCP and NMDA receptors. NIDA Research Monograph Series, pp 125–157Google Scholar
  191. Tokuyama S, Hirata K, Ide A, Ueda H (1997) Sigma ligands stimulate GTPase activity in mouse prefrontal membranes—evidence for the existence of metabotropic sigma receptor. Neurosci Lett 233:141–144CrossRefPubMedGoogle Scholar
  192. Tokuyama S, Hirata K, Yoshida A, Maruo J, Matsuno K, Mita S, Ueda H (1999) Selective coupling of mouse brain metabotropic sigma (σ) receptor with recombinant Gi1. Neurosci Lett 268:85–88CrossRefPubMedGoogle Scholar
  193. Torrence-Campbell C, Bowen WD (1996) Differential solubilization of rat liver sigma 1 and sigma 2 receptors: retention of sigma 2 sites in particulate fraction. Eur J Pharmacol 304:201–210CrossRefPubMedGoogle Scholar
  194. Tottori K, Miwa T, Uwahodo Y, Yamada S, Nakai M, Oshiro Y, Kikuchi T, Altar CA (2001) Antidepressant-like responses to the combined sigma and 5-HT1A receptor agonist OPC-14523. Neuropharmacology 41:976–988PubMedGoogle Scholar
  195. Tran TT, de Costa BR, Matsumoto RR (1998) Microinjection of sigma ligands into cranial nerve nuclei produces vacuous chewing in rats. Psychopharmacology 137:191–200CrossRefPubMedGoogle Scholar
  196. Uchida N, Ujike H, Nakata K, Takaki M, Nomura A, Katsu T, Tanaka Y, Imamura T, Sakai A, Kuroda S (2003) No association between the sigma receptor type 1 gene and schizophrenia: results of analysis and meta-analysis of case-control studies. BMC Psychiatry 3:13CrossRefPubMedGoogle Scholar
  197. Ujike H, Kanzaki A, Okumura K, Akiyama K, Otsuki S (1992) Sigma antagonist BMY 14802 prevents methamphetamine-induced sensitization. Life Sci 50:PL129–PL134CrossRefPubMedGoogle Scholar
  198. Ujike H, Kuroda S, Otsuki S (1996) Sigma receptor antagonists block the development of sensitization to cocaine. Eur J Pharmacol 296:123–128CrossRefPubMedGoogle Scholar
  199. Ukai M, Maeda H, Nanya Y, Kameyama T, Matsuno K (1998) Beneficial effects of acute and repeated administrations of sigma receptor agonists on behavioral despair in mice exposed to tail suspension. Pharmacol Biochem Behav 61:247–252PubMedGoogle Scholar
  200. Urani A, Roman FJ, Phan V-L, Su T-P, Maurice T (2001) The antidepressant-like effect induced by σ1-receptor agonists and neuroactive steroids in mice submitted to the forced swimming test. J Pharmacol Exp Ther 298:1269–1279PubMedGoogle Scholar
  201. Urani A, Romieu P, Portales-Casamar E, Roman FJ, Maurice T (2002) The antidepressant-like effect induced by the sigma1 (σ1) receptor agonist igmesine involves modulation of intracellular calcium mobilization. Psychopharmacology 163:26–35CrossRefPubMedGoogle Scholar
  202. Van Broekhoven F, Verkes RJ (2003) Neurosteroids in depression: a review. Psychopharmacology 165:97–110PubMedGoogle Scholar
  203. Vaupel DB (1983) Naltrexone fails to antagonize the sigma effects of PCP and SKF 10,047 in the dog. Eur J Pharmacol 92:269–274CrossRefPubMedGoogle Scholar
  204. Vilner BJ, Bowen WD (1993) Sigma receptor-active neuroleptics are cytotoxic to C6 glioma cells in culture. Eur J Pharmacol Mol Pharmacol Sect 244:199–201CrossRefGoogle Scholar
  205. Vilner BJ, Bowen WD (2000) Modulation of cellular calcium by sigma-2 receptors. Release from intracellular stores in human SK-N-SH neuroblastoma cells. J Pharmacol Exp Ther 292:900–911PubMedGoogle Scholar
  206. Vilner BJ, de Costa BR, Bowen WD (1995) Cytotoxic effects of sigma ligands: sigma receptor-mediated alterations in cellular morphology and viability. J Neurosci 15:117–134PubMedGoogle Scholar
  207. Walker JM, Bowen WD, Walker FO, Matsumoto RR, De Costa B, Rice KC (1990) Sigma receptors: biology and function. Pharmacol Rev 42:355–402Google Scholar
  208. Walker JM, Bowen WD, Patrick SL, Williams WE, Mascarella SW, Bai X, Carroll FI (1993) A comparison of (−)-deoxybenzomorphans devoid of opiate activity with their dextrorotatory phenolic counterparts suggests role of σ2 receptors in motor function. Eur J Pharmacol 231:61–68CrossRefPubMedGoogle Scholar
  209. Walker JM, Martin WJ, Hohmann AG, Hemstreet MK, Roth JS, Leitner ML, Weiser SD, Patrick SL, Patrick RL, Matsumoto RR (1994) Role of sigma receptors in brain mechanisms of movement. In: Itzhak Y (ed) Sigma receptors. Academic, San Diego, pp 205–224Google Scholar
  210. Weatherspoon JK, Werling LL (1999) Modulation of amphetamine-stimulated [3H]dopamine release from rat pheochromocytoma (PC12) cells by σ type 2 receptors. J Pharmacol Exp Ther 289:278–284PubMedGoogle Scholar
  211. Weber E, Sonders M, Quarum M, McLean S, Pou S, Keana JFW (1986) 1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels sigma-type receptors for psychotomimetic opiates and antipsychotic drugs. Proc Natl Acad Sci U S A 83:8784–8788PubMedGoogle Scholar
  212. Weissman AD, Casanova MF, Kleinman JE, London ED, De Souza EB (1991) Selective loss of cerebral cortical sigma but not PCP-binding sites in schizophrenia. Biol Psychiatry 29:41–54CrossRefPubMedGoogle Scholar
  213. Weissman AD, Su TP, Hedreen JC, London DE (1998) Sigma receptors in post-mortem human brains. J Pharmacol Exp Ther 247:29–33Google Scholar
  214. Wickman KD, Clapham DE (1995) G-protein regulation of ion channels. Curr Opin Neurobiol 5:278–285CrossRefPubMedGoogle Scholar
  215. Wilke RA, Mehta RP, Lupardus PJ, Chen Y, Ruoho AE, Jackson MB (1999a) Sigma receptor photolabeling and sigma receptor-mediated modulation of potassium channels in tumor cells. J Biol Chem 274:18387–18392CrossRefPubMedGoogle Scholar
  216. Wilke RA, Lupardus PJ, Grandy DK, Rubinstein M, Low MJ, Jackson MB (1999b) K+ channel modulation in rodent neurohypophysial nerve terminals by sigma receptors and not by dopamine receptors. J Physiol 517:391–406PubMedGoogle Scholar
  217. Yamada M, Nishigami T, Nakasho K, Nishimoto Y, Miyaji H (1994) Relationship between σ-like site and progesterone-binding site of adult male rat liver microsomes. Hepatology 20:1271–1280PubMedGoogle Scholar
  218. Yamamoto H, Miura R, Yamamoto T, Shinohara K, Watanabe M, Okuyama S, Nakazato A, Nukada T (1999) Amino acid residues in the transmembrane domain of the type 1 sigma receptor critical for ligand binding. FEBS Lett 445:19–22PubMedGoogle Scholar
  219. Yoshida K, Takahashi H, Sato K, Higuchi H, Shimizu T (2000) Biperiden hydrochlorate ameliorates dystonia of rats produced by microinjection of sigma ligands into the red nucleus. Pharmacol Biochem Behav 67:497–500CrossRefPubMedGoogle Scholar
  220. Ytzhak Y (1989) Multiple affinity binding states of the sigma receptor: effect of GTP-binding protein-modifying agents. Mol Pharmacol 36:512–517PubMedGoogle Scholar
  221. Zamanillo D, Andreu F, Ovalle S, Pérez MP, Romero G, Farré AJ, Guitart X (2000) Up-regulation of sigma1 receptor mRNA in rat brain by a putative atypical antipsychotic and sigma receptor ligand. Neurosci Lett 282:169–172PubMedGoogle Scholar
  222. Zamanillo D, Romero G, Dordal A, Pérez P, Vincent L, Méndez R, Andreu F, Hernández E, Pérez R, Monroy X, Ovalle S, Guitart X (2002) Increase of forskolin-stimulated adenylyl cyclase and AP-1 activities by sigma1 receptor expression. FENS Abstr A04617Google Scholar
  223. Zhang H, Cuevas J (2002) Sigma receptors inhibit high-voltage-activated calcium channels in rat sympathetic and parasympathetic neurons. J Neurophysiol 87:2867–2879PubMedGoogle Scholar
  224. Zou LB, Yamada K, Sasa M, Nakata Y, Nabeshima T (2000) Effects of sigma1 receptor agonist SA4503 and neuroactive steroids on performance in a radial arm maze task in rats. Neuropharmacology 39:1617–1627PubMedGoogle Scholar
  225. Zukin SR, Brady KT, Slifer BL, Balster RL (1984) Behavioral and biochemical stereoselectivity of sigma opiate/PCP receptors. Brain Res 294:174–177CrossRefPubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Biological Discovery and CNS Research DepartmentResearch CenterBarcelonaSpain

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