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The sigma-1 antagonist BMY-14802 inhibits L-DOPA-induced abnormal involuntary movements by a WAY-100635-sensitive mechanism

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An Erratum to this article was published on 01 April 2009

Abstract

Rationale

Levodopa (L-DOPA), the gold standard treatment for Parkinson’s disease (PD), eventually causes L-DOPA-induced dyskinesia (LID) in up to 80% of patients. In the 6-hydroxydopamine (6-OHDA) rat model of PD, L-DOPA induces a similar phenomenon, which has been termed abnormal involuntary movement (AIM). We previously demonstrated that BMY-14802 suppresses AIM expression in this model.

Objectives

Although BMY-14802 is widely used as a sigma-1 antagonist, it is also an agonist at serotonin (5-HT) 1A and adrenergic α-1 receptors. The current study was conducted to determine which of these mechanisms underlies BMY-14802’s AIM-suppressing effect. This characterization included testing the 5-HT1A agonist buspirone and multiple sigma agents. When these studies implicated a 5-HT1A mechanism, we subsequently undertook a pharmacological reversal study, evaluating whether the 5-HT1A antagonist WAY-100635 counteracted BMY-14802’s AIM-suppressing effects.

Results

Buspirone dose-dependently suppressed AIM, supporting past findings. However, no AIM-suppressing effects were produced by drugs with effects at sigma receptors, including BD-1047, finasteride, SM-21, DTG, trans-dehydroandrosterone (DHEA), carbetapentane, and opipramol. Finally, we show for the first time that the AIM-suppressing effect of BMY-14802 was dose-dependently prevented by WAY-100635 but not by the α-1 antagonist prazosin.

Conclusions

BMY-14802 exerts its AIM-suppressing effects via a 5-HT1A agonist mechanism, similar to buspirone. Other 5-HT1A agonists have failed clinical trials, possibly due to submicromolar affinity at other receptors, including D2, which may exacerbate PD symptoms. BMY-14802 is a promising candidate for clinical trials due to its extremely low affinity for the D2 receptor and lack of extrapyramidal effects during prior clinical trials for schizophrenia.

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References

  • Abou-Gharbia M, Patel UR, Webb MB, Moyer JA, Andree TH, Muth EA (1988) Polycyclic aryl- and heteroarylpiperazinyl imides as 5-HT1A receptor ligands and potential anxiolytic agents: synthesis and structure-activity relationship studies. J Med Chem 31:1382–1392

    Article  PubMed  CAS  Google Scholar 

  • Abou-Gharbia M, Moyer JA, Patel U, Webb M, Schiehser G, Andree T, Haskins JT (1989) Synthesis and structure-activity relationship of substituted tetrahydro- and hexahydro-1, 2-benzisothiazol-3-one 1, 1-dioxides and thiadiazinones: potential anxiolytic agents. J Med Chem 32:1024–1033

    Article  PubMed  CAS  Google Scholar 

  • Ahlenius S, Hillegaart V, Wijkström A (1990) Increased dopamine turnover in the ventral striatum by 8-OH-DPAT administration in the rat. J Pharm Pharmacol 42(4):285–288

    PubMed  CAS  Google Scholar 

  • Alex KD, Pehek EA (2007) Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharm & Ther 113:296–320

    Article  CAS  Google Scholar 

  • Antonelli T, Fuxe K, Tomasini MC, Bartoszyk GD, Seyfried CA, Tanganelli S, Ferraro L (2005) Effects of sarizotan on the corticostriatal glutamate pathways. Synapse 58:193–199

    Article  PubMed  CAS  Google Scholar 

  • Ba M, Kong M, Ma G, Yang H, Lu G, Chen S, Liu Z (2006) Cellular and behavioral effects of 5-HT1A receptor agonist 8-OH-DPAT in a rat model of L-DOPA-induced motor complications. Brain Res 1127:177–184

    Article  PubMed  CAS  Google Scholar 

  • Bardin L, Kleven MS, Barret-Grévoz C, Depoortère R, Newman-Tancredi A (2006) Antipsychotic-like vs cataleptogenic actions in mice of novel antipsychotics having D2 antagonist and 5-HT1A agonist properties. Neuropsychopharmacology 31:1869–1879

    Article  PubMed  CAS  Google Scholar 

  • Bartoszyk GD, Bender H, Hellmann J, Schnorr C, Seyfried CA (1996) EMD 57445: a selective sigma receptor ligand with the profile of an atypical neuroleptic. CNS Drug Rev 2:175–196

    Article  CAS  Google Scholar 

  • Bédard MA, el Massioui F, Malapani C, Dubois B, Pillon B, Renault B, Agid Y (1998) Attentional deficits in Parkinson’s disease: partial reversibility with naphtoxazine (SDZ NVI-085), a selective noradrenergic alpha 1 agonist. Clin Neuropharmacol 21:108–117

    PubMed  Google Scholar 

  • Bevilacqua M, Vago T, Monopoli A, Baldi G, Forlani A, Antona C, Biglioli P, Scrofani R, Norbiato G (1991) Alpha 1 adrenoceptor subtype mediates noradrenaline induced contraction of the human internal mammary artery: radioligand and functional studies. Cardiovasc Res 25:290–294

    Article  PubMed  CAS  Google Scholar 

  • Bhidayasiri R, Truong DD (2008) Motor complications in Parkinson disease: clinical manifestations and management. J Neurol Sci 266:204–215

    Article  PubMed  Google Scholar 

  • Bibbiani F, Oh JD, Chase TN (2001) Serotonin 5-HT1A agonist improves motor complications in rodent and primate parkinsonian models. Neurology 57:1829–1834

    PubMed  CAS  Google Scholar 

  • Bishnoi M, Chopra K, Kulkarni SK (2008) Progesterone attenuates neuroleptic-induced orofacial dyskinesia via the activity of its metabolite, allopregnanolone, a positive GABA(A) modulating neurosteroid. Prog Neuropsychopharmacol Biol Psychiatry 32:451–461

    Article  PubMed  CAS  Google Scholar 

  • Blanchet PJ, Papa SM, Metman LV, Mouradian MM, Chase TN (1997) Modulation of levodopa-induced motor response complications by NMDA antagonists in Parkinson’s disease. Neurosci Biobehav Rev 21:447–453

    Article  PubMed  CAS  Google Scholar 

  • Bonifati V, Fabrizio E, Cipriani R, Vanacore N, Meco G (1994) Buspirone in levodopa-induced dyskinesias. Clin Neuropharmacol 17:73–82

    Article  PubMed  CAS  Google Scholar 

  • Bristow LJ, Baucutt L, Thorn L, Hutson PH, Noble A, Beer M, Middlemiss DN, Tricklebank MD (1991) Behavioural and biochemical evidence of the interaction of the putative antipsychotic agent, BMY 14802 with the 5-HT1A receptor. Eur J Pharmacol 204:21–28

    Article  PubMed  CAS  Google Scholar 

  • Calderon SN, Izenwasser S, Heller B, Gutkind JS, Mattson MV, Su TP, Newman AH (1994) Novel 1-phenylcycloalkanecarboxylic acid derivatives are potent and selective sigma 1 ligands. J Med Chem 37:2285–2291

    Article  PubMed  CAS  Google Scholar 

  • Callahan PM, Cunningham KA (1997) Modulation of the discriminative stimulus properties of cocaine: comparison of the effects of fluoxetine with 5-HT1A and 5-HT1B receptor agonists. Neuropharmacology 36:373–381

    Article  PubMed  CAS  Google Scholar 

  • Canales JJ, Graybiel AM (2000) Patterns of gene expression and behavior induced by chronic dopamine treatments. Ann Neurol 47(4 Suppl 1):S53–S59

    PubMed  CAS  Google Scholar 

  • Chan DK, Cordato DJ, O’Rourke F (2008) Management for motor and non-motor complications in late Parkinson’s disease. Geriatrics 63:22–27

    PubMed  Google Scholar 

  • Chang JW, Wachtel SR, Young D, Kang UJ (1999) Biochemical and anatomical characterization of forepaw adjusting steps in rat models of Parkinson’s disease: studies on medial forebrain bundle and striatal lesions. Neuroscience 88:612–628

    Article  Google Scholar 

  • Chen L, Yung KK, Chan YS, Yung WH (2008) 5-HT excites globus pallidus neurons by multiple receptor mechanisms. Neuroscience 151:439–451

    Article  PubMed  CAS  Google Scholar 

  • Cenci MA, Lee CS, Bjorklund A (1998) L-DOPA-induced dyskinesia in the rat is associated with striatal overexpression of prodynorphin- and glutamic acid decarboxylase mRNA. Eur J Neurosci 10:2694–2706

    Article  PubMed  CAS  Google Scholar 

  • Cobb WS, Abercrombie ED (2003) Differential regulation of somatodendritic and nerve terminal dopamine release by serotonergic innervation of substantia nigra. J Neurochem 84:576–584

    Article  PubMed  CAS  Google Scholar 

  • Dekundy A, Pietraszek M, Schaefer D, Cenci MA, Danysz W (2006) Effects of group I metabotropic glutamate receptors blockade in experimental models of Parkinson’s disease. Brain Res Bull 69:318–326

    Article  PubMed  CAS  Google Scholar 

  • Dekundy A, Lundblad M, Danysz W, Cenci MA (2007) Modulation of L-DOPA-induced abnormal involuntary movements by clinically tested compounds. Beh Brain Res 179:76–89

    Article  CAS  Google Scholar 

  • Del Dotto P, Pavese N, Gambaccini G, Bernardini S, Metman LV, Chase TN, Bonuccelli U (2001) Intravenous amantadine improves levadopa-induced dyskinesias: an acute double-blind placebo-controlled study. Mov Disorders 16:515–520

    Article  Google Scholar 

  • Di Giovanni G, Di Matteo V, Pierucci M, Benigno A, Esposito E (2006) Serotonin involvement in the basal ganglia pathophysiology: could the 5-HT2C receptor be a new target for therapeutic strategies? Curr Med Chem 13:3069–3081

    Article  PubMed  Google Scholar 

  • Dupre KB, Eskow KL, Negron G, Bishop C (2007) The differential effects of 5-HT(1A) receptor stimulation on dopamine receptor-mediated abnormal involuntary movements and rotations in the primed hemiparkinsonian rat. Brain Res 1158:135–143

    Article  PubMed  CAS  Google Scholar 

  • Dupre KB, Eskow KL, Steiniger A, Klioueva A, Negron GE, Lormand L, Park JY, Bishop C (2008) Effects of coincident 5-HT(1A) receptor stimulation and NMDA receptor antagonism on L-DOPA-induced dyskinesia and rotational behaviors in the hemi-parkinsonian rat. Psychopharmacology (Berl.) 199:99–108

    Article  CAS  Google Scholar 

  • Eglen RM, Jasper JR, Chang DJ, Martin GR (1997) The 5-HT7 receptor: orphan found. Trends Pharmacol Sci 18:104–107

    Article  PubMed  CAS  Google Scholar 

  • Eskow KL, Gupta V, Alam S, Park JY, Bishop C (2007) The partial 5-HT(1A) agonist buspirone reduces the expression and development of L-DOPA-induced dyskinesia in rats and improves L-DOPA efficacy. Pharmacol Biochem Behav 87:306–314

    Article  PubMed  CAS  Google Scholar 

  • Fabbrini G, Brotchie JM, Grandas F, Nomoto M, Goetz CG (2007) Levodopa-induced dyskinesias. Mov Disord 22:1379–1389

    Article  PubMed  Google Scholar 

  • Feldstein JB, Pacitti AJ, Sumners C, Raizada MK (1986) Alpha 1-adrenergic receptors in neuronal cultures from rat brain: increased expression in the spontaneously hypertensive rat. J Neurochem 47:1190–1198

    PubMed  CAS  Google Scholar 

  • Frechilla D, Cobreros A, Saldise L, Moratalla R, Insausti R, Luquin M, Del Río J (2001) Serotonin 5-HT(1A) receptor expression is selectively enhanced in the striosomal compartment of chronic parkinsonian monkeys. Synapse 39:288–296

    Article  PubMed  CAS  Google Scholar 

  • Frieboes RM, Murck H, Wiedemann K, Holsboer F, Steiger A (1997) Open clinical trial on the sigma ligand panamesine in patients with schizophrenia. Psychopharmacology (Berl.) 132:82–88

    Article  CAS  Google Scholar 

  • Frye CA, Walf AA (2002) Changes in progesterone metabolites in the hippocampus can modulate open field and forced swim test behavior of proestrous rats. Horm Behav 41:306–315

    Article  PubMed  CAS  Google Scholar 

  • 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 10:37–40

    PubMed  CAS  Google Scholar 

  • Ghelardini C, Galeotti N, Gualtieri F, Bellucci C, Manetti D, Giotti A, Malmberg-Aiello P, Galli A, Bartolini A (1997) Antinociceptive profile of 3-alpha-tropanyl 2-(4-Cl-phenoxy) butyrate (SM-21) [corrected]: a novel analgesic with a presynaptic cholinergic mechanism of action. J Pharmacol Exp Ther 282:430–439

    PubMed  CAS  Google Scholar 

  • Goetz CG, Damier P, Hicking C, Laska E, Müller T, Olanow CW, Rascol O, Russ H (2007) Sarizotan as a treatment for dyskinesias in Parkinson’s disease: a double-blind placebo-controlled trial. Mov Disord 22:179–186

    Article  PubMed  Google Scholar 

  • Hajós-Korcsok E, Sharp T (1996) 8-OH-DPAT-induced release of hippocampal noradrenaline in vivo: evidence for a role of both 5-HT1A and dopamine D1 receptors. Eur J Pharmacol 314:285–291

    Article  PubMed  Google Scholar 

  • Halkias IA, Haq I, Huang Z, Fernandez HH (2007) When should levodopa therapy be initiated in patients with Parkinson’s disease? Drugs Aging 24:261–273

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto K, Kita H (2008) Serotonin activates presynaptic and postsynaptic receptors in rat globus pallidus. J Neurophysiol 99:1723–1732

    Article  PubMed  CAS  Google Scholar 

  • Holoubek G, Müller WE (2003) Specific modulation of sigma binding sites by the anxiolytic drug opipramol. J Neural Transm 110:1169–1179

    Article  PubMed  CAS  Google Scholar 

  • Huber MT, Gotthardt U, Schreiber W, Krieg JC (1999) Efficacy and safety of the sigma receptor ligand EMD 57445 (panamesine) in patients with schizophrenia: an open clinical trial. Pharmacopsychiatry 32:68–72

    Article  PubMed  CAS  Google Scholar 

  • Iravani MM, Tayarani-Binazir K, Chu WB, Jackson MJ, Jenner P (2006) In 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-treated primates, the selective 5-hydroxytryptamine 1A agonist (R)-(+)-8-OHDPAT inhibits levodopa-induced dyskinesia but only with increased motor disability. J Pharmacol Exp Ther 319:1225–1234

    Article  PubMed  CAS  Google Scholar 

  • Kannari K, Yamato H, Shen H, Tomiyama M, Suda T, Matsunaga M (2001) Activation of 5-HT(1A) but not 5-HT(1B) receptors attenuates an increase in extracellular dopamine derived from exogenously administered L-DOPA in the striatum with nigrostriatal denervation. J Neurochem 76:1346–1353

    Article  PubMed  CAS  Google Scholar 

  • Kannari K, Kurahashi K, Tomiyama M, Maeda T, Arai A, Baba M, Suda T, Matsunaga M (2002) Tandospirone citrate, a selective 5-HT1A agonist, alleviates L-DOPA-induced dyskinesia in patients with Parkinson’s disease. No To Shinkei 54:133–137

    PubMed  Google Scholar 

  • Kelland MD, Freeman AS, Chiodo LA (1990) Serotonergic afferent regulation of the basic physiology and pharmacological responsiveness of nigrostriatal dopamine neurons. J Pharmacol Exp Ther 253:803–811

    PubMed  CAS  Google Scholar 

  • Kleven M, Prinssen EP, Koek W (1996) Role of 5-HT1A receptors in the ability of mixed 5-HT1A receptor agonist/dopamine D2 receptor antagonists to inhibit methylphenidate-induced behaviors in rats. Eur J Pharmacol 313:25–34

    Article  PubMed  CAS  Google Scholar 

  • Kleven MS, Barret-Grévoz C, Bruins Slot L, Newman-Tancredi A (2005) Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats. Neuropharmacology 49:135–143

    Article  PubMed  CAS  Google Scholar 

  • Kuzhikandathil EV, Bartoszyk GD (2006) The novel antidyskinetic drug sarizotan elicits different functional responses at human D2-like dopamine receptors. Neuropharmacology 51:873–884

    Article  PubMed  CAS  Google Scholar 

  • Leander JD (1989) Evaluation of dextromethorphan and carbetapentane as anticonvulsants and N-methyl-D-aspartic acid antagonists in mice. Epilepsy Res 4:28–33

    Article  PubMed  CAS  Google Scholar 

  • Levandis G, Bazzini E, Armentero MT, Nappi G, Blandini F (2008) Systemic administration of an mGluR5 antagonist, but not unilateral subthalamic lesion, counteracts l-DOPA-induced dyskinesias in a rodent model of Parkinson’s disease. Neurobiol Dis 29:161–168

    Article  PubMed  CAS  Google Scholar 

  • Lever JR, Gustafson JL, Xu R, Allmon RL, Lever SZ (2006) Sigma1 and sigma2 receptor binding affinity and selectivity of SA4503 and fluoroethyl SA4503. Synapse 59:350–358

    Article  PubMed  CAS  Google Scholar 

  • Lundblad M, Andersson M, Winkler C, Kirik D, Wierup N, Cenci MA (2002) Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson’s disease. Eur J Neurosci 15:120–132

    Article  PubMed  CAS  Google Scholar 

  • Lundblad M, Usiello A, Carta M, Hkanssond K, Fisoned G, Cenci MA (2005) Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia. Exp Neurol 194:66–75

    Article  PubMed  CAS  Google Scholar 

  • Matos FF, Korpinen C, Yocca FD (1996) 5-HT1A receptor agonist effects of BMY-14802 on serotonin release in dorsal raphe and hippocampus. Eur J Pharmacol 12(317):49–54

    Article  Google Scholar 

  • Matsumoto RR, Bowen WD, Tom MA, Vo VN, Truong DD, De Costa BR (1995) Characterization of two novel sigma receptor ligands: antidystonic effects in rats suggest sigma receptor antagonism. Eur J Pharmacol 280:301–310

    Article  PubMed  CAS  Google Scholar 

  • Matsumoto RR, Pouw B, Mack AL, Daniels A, Coop A (2007) Effects of UMB24 and (+/-)-SM 21, putative sigma2-preferring antagonists, on behavioral toxic and stimulant effects of cocaine in mice. Pharmacol Biochem Behav 86:86–91

    Article  PubMed  CAS  Google Scholar 

  • Matthews RT, McMillen BA, Sallis R, Blair D (1986) Effects of BMY 14802, a potential antipsychotic drug, on rat brain dopaminergic function. J Pharmacol Exp Ther 239:124–131

    PubMed  CAS  Google Scholar 

  • Matuszewich L, Lorrain DS, Trujillo R, Dominguez J, Putnam SK, Hull EM (1999) Partial antagonism of 8-OH-DPAT’S effects on male rat sexual behavior with a D2, but not a 5-HT1A, antagonist. Brain Res 820:55–62

    Article  PubMed  CAS  Google Scholar 

  • Mavridis M, Colpaert FC, Millan MJ (1991) Differential modulation of (+)-amphetamine-induced rotation in unilateral substantia nigra-lesioned rats by alpha 1 as compared to alpha 2 agonists and antagonists. Brain Res 562:216–224

    Article  PubMed  CAS  Google Scholar 

  • McPherson GA, Summers RJ (1982) A study of alpha 1-adrenoceptors in rat renal cortex: comparison of [3H]-prazosin binding with the alpha 1-adrenoceptor modulating gluconeogenesis under physiological conditions. Br J Pharmacol 77:177–184

    PubMed  CAS  Google Scholar 

  • Mela F, Marti M, Dekundy A, Danysz W, Morari M, Cenci MA (2007) Antagonism of metabotropic glutamate receptor type 5 attenuates l-DOPA-induced dyskinesia and its molecular and neurochemical correlates in a rat model of Parkinson’s disease. J Neurochem 101:483–497

    Article  PubMed  CAS  Google Scholar 

  • Mignon LJ, Wolf WA (2005) 8-hydroxy-2-(di-n-propylamino) tetralin reduces striatal glutamate in an animal model of Parkinson’s disease. NeuroReport 16:699–703

    Article  PubMed  CAS  Google Scholar 

  • Miller SC (2005) Dextromethorphan psychosis, dependence and physical withdrawal. Addict Biol 10:325–327

    Article  PubMed  CAS  Google Scholar 

  • Modell S, Naber D, Holzbach R (1996) Efficacy and safety of an opiate sigma-receptor antagonist (SL 82.0715) in schizophrenic patients with negative symptoms: an open dose-range study. Pharmacopsychiatry 29:63–66

    Article  PubMed  CAS  Google Scholar 

  • Müller MJ, Gründer G, Wetzel H, Müller-Siecheneder F, Marx-Dannigkeit P, Benkert O (1999) Antipsychotic effects and tolerability of the sigma ligand EMD 57445 (panamesine) and its metabolites in acute schizophrenia: an open clinical trial. Psychiatry Res 89:275–280

    Article  PubMed  Google Scholar 

  • Mura A, Mintz M, Feldon J (2002) Behavioral and anatomical effects of long-term L-dihydroxyphenylalanine (L-DOPA) administration in rats with unilateral lesions of the nigrostriatal system. Exp Neurol 177:252–264

    Article  PubMed  CAS  Google Scholar 

  • Nutt JG (2000) Clinical pharmacology of levodopa-induced dyskinesia. Ann Neurol 47(4 Suppl 1):S160–S164

    PubMed  CAS  Google Scholar 

  • Okumura K, Ujike H, Akiyama K, Kuroda S (1996) BMY-14802 reversed the sigma receptor agonist-induced neck dystonia in rats. J Neural Transm 103:1153–1161

    Article  PubMed  CAS  Google Scholar 

  • Olanow CW, Damier P, Goetz CG, Mueller T, Nutt J, Rascol O, Serbanescu A, Deckers F, Russ H (2004) Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa-induced dyskinesias (the SPLENDID Study). Clin Neuropharmacol 27:58–62

    Article  PubMed  CAS  Google Scholar 

  • Papa SM, Chase TN (1996) Levodopa-induced dyskinesias improved by a glutamate antagonist in Parkinsonian monkeys. Ann Neurol 39:574–578

    Article  PubMed  CAS  Google Scholar 

  • Paquette MA, Brudney EG, Putterman DB, Meshul CK, Johnson SW, Berger SP (2008) Sigma ligands, but not N-methyl-D-aspartate antagonists, reduce levodopa-induced dyskinesias. NeuroReport 19:111–115

    Article  PubMed  CAS  Google Scholar 

  • Patrick SL, Walker JM, Perkel JM, Lockwood M, Patrick RL (1993) Increases in rat striatal extracellular dopamine and vacuous chewing produced by two sigma receptor ligands. Eur J Pharmacol 231:243–249

    Article  PubMed  CAS  Google Scholar 

  • Peroutka SJ (1985) Selective interaction of novel anxiolytics with 5-hydroxytryptamine1A receptors. Biol Psychiatry 20:971–979

    Article  PubMed  CAS  Google Scholar 

  • Perrone R, Berardi F, Colabufo NA, Tortorella V, Fiorentini F, Olgiati V, Vanotti E, Govoni S (1994) Mixed 5-HT1A/D-2 activity of a new model of arylpiperazines: 1-aryl-4-[3-(1, 2-dihydronaphthalen-4-yl)-n-propyl]piperazines 1. Synthesis and structure-activity relationships. J Med Chem 37:99–104

    Article  PubMed  CAS  Google Scholar 

  • Rao TS, Cler JA, Mick SJ, Dilworth VM, Contreras PC, Iyengar S, Wood PL (1990) Neurochemical characterization of dopaminergic effects of opipramol, a potent sigma receptor ligand, in vivo. Neuropharmacology 29:1191–1197

    Article  PubMed  CAS  Google Scholar 

  • Romieu P, Martin-Fardon R, Maurice T (2000) Involvement of the σ1 receptor in the cocaine-induced conditioned place preference. NeuroReport 11:2885–2888

    Article  PubMed  CAS  Google Scholar 

  • Romieu P, Martin-Fardon R, Bowen WD, Maurice T (2003) Sigma 1 receptor-related neuroactive steroids modulate cocaine-induced reward. J Neurosci 23:3572–3576

    PubMed  CAS  Google Scholar 

  • Romieu P, Meunier J, Garcia D, Zozime N, Martin-Fardon R, Bowen WD, Maurice T (2004) The sigma1 (sigma1) receptor activation is a key step for the reactivation of cocaine conditioned place preference by drug priming. Psychopharmacology (Berl) 175:154–162

    Article  CAS  Google Scholar 

  • Sánchez A, Torres A, Sáiz J (1989) Renal alpha-adrenoceptor density and blood pressure in SHR rats exposed chronically to prazosin and/or yohimbine. Clin Exp Hypertens A 11:119–136

    Article  PubMed  Google Scholar 

  • Schoemaker H, Langer SZ (1986) [3H]8-OH-DPAT labels the serotonin transporter in the rat striatum. Eur J Pharmacol 124:371–373

    Article  PubMed  CAS  Google Scholar 

  • Skuza G, Kolasiewicz W, Dziedzicka-Wasylewska M, Margas W (1998) Effect of local intracerebral administration of EMD 57445, a selective sigma receptor ligand, on the locomotor activity of the rat. Pol J Pharmacol 50:399–406

    PubMed  CAS  Google Scholar 

  • Solomon RE, Brody MJ, Gebhart GF (1989) Pharmacological characterization of alpha adrenoceptors involved in the antinociceptive and cardiovascular effects of intrathecally administered clonidine. J Pharmacol Exp Ther 251:27–38

    PubMed  CAS  Google Scholar 

  • Stanford IM, Kantaria MA, Chahal HS, Loucif KC, Wilson CL (2005) 5-Hydroxytryptamine induced excitation and inhibition in the subthalamic nucleus: action at 5-HT(2C), 5-HT(4) and 5-HT(1A) receptors. Neuropharmacology 49:1228–1234

    Article  PubMed  CAS  Google Scholar 

  • Stefanski R, Justinova Z, Hayashi T, Takebayashi M, Goldberg SR, Su TP (2004) Sigma(1) receptor upregulation after chronic methamphetamine self-administration in rats: a study with yoked controls. Psychopharmacology (Berl) 75:68–75

    Google Scholar 

  • Taylor JL, Bishop C, Walker PD (2005) Dopamine D1 and D2 receptor contributions to L-DOPA-induced dyskinesia in the dopamine-depleted rat. Pharmacol Biochem Behav 81:887–893

    Article  PubMed  CAS  Google Scholar 

  • Temel Y, Boothman LJ, Blokland A, Magill PJ, Steinbusch HW, Visser-Vandewalle V, Sharp T (2007) Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus. Proc Natl Acad Sci USA 104:17087–17092

    Article  PubMed  CAS  Google Scholar 

  • Thomas A, Iacono D, Luciano AL, Armellino K, Di Iorio A, Onofrj M (2004) Duration of amantadine benefit on dyskinesia of severe Parkinson’s disease. J Neurol Neurosurg Psychiatry 75:141–143

    PubMed  CAS  Google Scholar 

  • Tomiyama M, Kimura T, Maeda T, Kannari K, Matsunaga M, Baba M (2005) A serotonin 5-HT1A receptor agonist prevents behavioral sensitization to L-DOPA in a rodent model of Parkinson’s disease. Neurosci Res 52:185–194

    Article  PubMed  CAS  Google Scholar 

  • Tsou AP, Kosaka A, Bach C, Zuppan P, Yee C, Tom L, Alvarez R, Ramsey S, Bonhaus DW, Stefanich E, Jakeman L, Eglen RM (1994) Cloning and expression of a 5-hydroxytryptamine 7 receptor positively coupled to adenylyl cyclase. J Neurochem 63:456–464

    Article  PubMed  CAS  Google Scholar 

  • Ujike H, Kanzaki A, Okumura K, Akiyama K, Otsuki S (1992a) Sigma (σ) antagonist BMY-14802 prevents methamphetamine-induced sensitization. Life Sci 50:PL129–PL134

    Article  PubMed  CAS  Google Scholar 

  • Ujike H, Okamura K, Zushi Y, Akiyama K, Otsuki S (1992b) Persistent supersensitivity of sigma receptors develops during repeated methamphetamine treatment. Eur J Pharmacology 211:323–328

    Article  CAS  Google Scholar 

  • Ujike H, Tsuchida K, Akiyama K, Otsuki S (1992c) Supersensitivity of sigma receptors after repeated administration of cocaine. Life Sci 51:PL31–PL36

    Article  PubMed  CAS  Google Scholar 

  • Ujike H, Kuroda A, Orauki A (1996) σ receptor antagonists block the development of sensitization to cocaine. Eur J Pharmacol 296:123–128

    Article  PubMed  CAS  Google Scholar 

  • VanderMaelen CP, Braselton JP (1990) Effects of a potential antipsychotic, BMY 14802, on firing of central serotonergic and noradrenergic neurons in rats. Eur J Pharmacol 179:357–366

    Article  PubMed  CAS  Google Scholar 

  • Vanecek SA, Essman WD, Taylor DP, Woods JH (1998) Discriminative stimulus characteristics of BMY 14802 in the pigeon. J Pharmacol Exp Ther 284:1–9

    PubMed  CAS  Google Scholar 

  • Verhagen-Metman L, Del Dotto P, Blanchet PJ, van den Munckhof P, Chase TN (1998) Blockade of glutamatergic transmission as treatment for dyskinesias and motor fluctuations in PD. Amino Acids 14:75–82

    Article  PubMed  CAS  Google Scholar 

  • Verhagen Metman L, Del Dotto P, van den Munckhof P, Fang J, Mouradian MM, Chase TN (1998) Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson’s disease. Neurology 50:1323–1326

    PubMed  CAS  Google Scholar 

  • Waterhouse RN, Chang RC, Atuehene N, Collier TL (2007) In vitro and in vivo binding of neuroactive steroids to the sigma-1 receptor as measured with the positron emission tomography radioligand [18F]FPS. Synapse 61:540–546

    Article  PubMed  CAS  Google Scholar 

  • Wood M, Chaubey M, Atkinson P, Thomas DR (2000) Antagonist activity of meta-chlorophenylpiperazine and partial agonist activity of 8-OH-DPAT at the 5-HT7 receptor. Eur J Pharmacol 396:1–8

    Article  PubMed  CAS  Google Scholar 

  • Xiang Z, Wang L, Kitai ST (2005) Modulation of spontaneous firing in rat subthalamic neurons by 5-HT receptor subtypes. J Neurophysiol 93:1145–1157

    Article  PubMed  CAS  Google Scholar 

  • Yen MH, Sheu JR, Peng IH, Lee YM, Chern JW (1996) Pharmacological activity of DC-015, a novel potent and selective alpha 1-adrenoceptor antagonist. J Pharm Pharmacol 48:90–95

    PubMed  CAS  Google Scholar 

  • Yevich JP, New JS, Lobeck WG, Dextraze P, Bernstein E, Taylor DP, Yocca FD, Eison MS, Temple DL Jr (1992) Synthesis and biological characterization of alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol and analogues as potential atypical antipsychotic agents. J Med Chem 35:4516–4525

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Chiodo LA, Freeman AS (1993) Further characterization of the effects of BMY 14802 on dopamine neuronal activity. Synapse 15:276–284

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, 97239, USA

    Melanie A. Paquette, Charles K. Meshul & S. Paul Berger

  2. Department of Neurology, Oregon Health and Science University, Portland, OR, 97239, USA

    Melanie A. Paquette & Steven W. Johnson

  3. Department of Veterans Affairs Medical Center, 3710 SW US Veterans Hospital Road, Mail Code R&D 64, Portland, OR, 97239, USA

    Melanie A. Paquette, Katherine Foley, Elizabeth G. Brudney, Charles K. Meshul, Steven W. Johnson & S. Paul Berger

Authors
  1. Melanie A. Paquette
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  2. Katherine Foley
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  3. Elizabeth G. Brudney
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  4. Charles K. Meshul
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  5. Steven W. Johnson
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  6. S. Paul Berger
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Corresponding author

Correspondence to Melanie A. Paquette.

Additional information

Funding was provided by NIDA DA007262-16 (MAP), NINDS NS38715 (SJW), and Veterans Affairs Merit Reviews (CKM and SPB).

An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-009-1522-7

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Paquette, M.A., Foley, K., Brudney, E.G. et al. The sigma-1 antagonist BMY-14802 inhibits L-DOPA-induced abnormal involuntary movements by a WAY-100635-sensitive mechanism. Psychopharmacology 204, 743–754 (2009). https://doi.org/10.1007/s00213-009-1505-8

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  • DOI: https://doi.org/10.1007/s00213-009-1505-8

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