Journal of Neural Transmission

, Volume 103, Issue 10, pp 1153–1161 | Cite as

BMY-14802 reversed the σ receptor agonist-induced neck dystonia in rats

  • K. Okumura
  • H. Ujike
  • K. Akiyama
  • S. Kuroda
Basic Neurosciences and Genetics
Received:
Accepted:

Summary

To clarify clinical roles of σ receptor binding affinity of neuroleptics, neck dystonia induced by microinjection of σ receptor ligands and neuroleptics into rat red nucleus was investigated. DTG and (+)-3-PPP, putative σ receptor agonists, induced neck dystonia in dose-dependent and reversible manner. Haloperidol and perphenazine induced dystonia in the same way as σ receptor agonists, whereas zotepine and (−)-sulpiride did not. The rank order of potency in induction of dystonia and σ receptor affinity of these compounds showed positive correlation. Although BMY-14802 has a high affinity for σ receptors, it never produced dystonia by itself. On the other hand, combined injection of BMY-14802 with DTG attenuated DTG-induced dystonia. Therefore, it is suggested that typical neuroleptics such as haloperidol act agonistic and atypical neuroleptics such as BMY-14802 act antagonistic at rubral σ receptors in the induction of neck dystonia.

Keywords

Sigma receptors neck dystonia red nucleus BMY-14802 neuroleptics 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bowen WD, Walker JM, Yashar AG, Matsumoto RR, Walker FO, Lorden JF (1988) Altered haloperidol-sensitive sigma receptors in the genetically dystonic (dt) rat. Eur J Pharmacol 147: 153–154Google Scholar
  2. 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: 21–28Google Scholar
  3. Chouinard G, Annable L (1984) An early phase II clinical trial of BW234U in the treatment of acute schizophrenia in newly admitted patients. Psychopharmacology (Berl) 84: 282–284Google Scholar
  4. Ferris CD, Hirsch DJ, Brooks BP, Snyder SH (1991) σReceptors: from molecule to man. J Neurochem 57: 729–737Google Scholar
  5. Ferris RM, Harfenist M, McKenzie GM, Cooper B, Soroko FE, Maxwell RA (1982) BW 234U, (cis-9-[3,5-dimethyl-1-piperazinyl)propyl]carbazole dihydrochloride): a novel antipsychotic agent. J Pharm Pharmacol 34: 388–390Google Scholar
  6. 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: 37–40Google Scholar
  7. Gundlach AL, Largent BL, Snyder SH (1986) Autoradiographic localization of σ receptor binding sites in guinea pig and rat central nervous system with (+)3H-3-(3-hydroxyphenyl)-N-(l-propyl)piperidine. J Neurosci 6: 1757–1770Google Scholar
  8. Guy W, Manov G, Wilson WH, Ban TA, Fjetland OK, Manberg PJ, Dren AT (1983) Psychotropic action of BW 234U in the treatment of inpatient schizophrenics: a doserange study. Drug Dev Res 3: 245–252Google Scholar
  9. Lapierre YD, Ancill R, Awad G, Bakish D, Beaudry P, Bloom D, Chandrasena R, Das M, Durand C, Elliott D (1992) A dose-finding study with remoxipride in the acute treatment of schizophrenic patients. J Psychiatr Neurosci 17: 134–145Google Scholar
  10. Largent BL, Gundlach AL, Snyder SH (1986) Pharmacological and autoradi-ographic discrimination of σ 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: 739–748Google Scholar
  11. Largent BL, Wikstrom H, Snowman AM, Snyder SH (1988) Novel antipsychotic drugs share high affinity for σ receptors. Eur J Pharmacol 155: 345–347Google Scholar
  12. Lindstrom L, Besev G, Stening G, Widerlov E (1985) An open study of remoxipride, a benzamide derivative, in schizophrenia. Psychopharmacology 86: 241–243Google Scholar
  13. 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: 124–131Google Scholar
  14. McCreadie RG, Morrison D, Eccleston D, Gall RG, Loudon J, Mitchell MJ (1985) An open multicentre study of the treatment of florid schizophrenia with remoxipride. Acta Psychiatr Scand 72: 139–143Google Scholar
  15. Ogren SO, Hall H, Kohler C, Magnusson O, Lindbom LO, Angeby K, Florvall L (1984) Remoxipride, a new potential antipsychotic compound with selective antidopaminergic actions in the rat brain. Eur J Pharmacol 102: 459–474Google Scholar
  16. Patris M, Agussol P, Alby JM, Brion S, Burnat G, Castelnau D, Deluermoz S, Dufour H, Ferreri M, Goudemand M (1990) A double-blind multicentre comparison of remoxipride, at two dose levels, and haloperidol. Acta Psychiatr Scand [Suppl] 358: 78–82Google Scholar
  17. Pazos A, Palacios JM (1985) Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors. Brain Res 346: 205–230Google Scholar
  18. Rupniak NMJ, Jenner P, Marsden CD (1986) Acute dystonia induced by neuroleptic drugs. Psychopharmacology 88: 403–419Google Scholar
  19. Schwarcz G, Halaris A, Dren A, Manberg P (1985) Open label evaluation of the novel antipsychotic compound BW234U in chronic schizophrenics. Drug Dev Res 5: 387–393Google Scholar
  20. Su TP (1991) σ receptors. Putative links between nervous, endocrine and immune systems. Eur J Biochem 200: 633–642Google Scholar
  21. Taylor DP, Eison MS, Moon SL, Yocca FD (1991) BMY 14802, a potential antipsychotic with selective affinity for σ-binding sites. In: Tamminga CA, Schulz SC (eds) Advances in neuropsychiatry and psychopharmacology, 1. Schizophrenia research. Raven Press, New York, pp 307–315Google Scholar
  22. Walker JM, Matsumoto RR, Bowen WD, Gans DL, Jones KD, Walker FO (1988) Evidence for a role of haloperidol-sensitive σ-“opiate” receptors in the motor effects of antipsychotic drugs. Neurology 38: 961–965Google Scholar
  23. Walker JM, Bowen WD, Walker FO, Matsumoto RR, De CB, Rice KC (1990) Sigma receptors: biology and function. Pharmacol Rev 42: 355–402Google Scholar
  24. Weber E, Sonders M, Quarum M, McLean S, Pou S, Keana JF (1986) 1,3-Di(2-[5-3H]tolyl)guanidine: a selective ligand that labels σ-type receptors for psychotomimetic opiates and antipsychotic drugs. Proc Natl Acad Sci USA 83: 8784–8788Google Scholar
  25. Yevich JP, New JS, Smith DW, Lobeck WG, Catt JD, Minielli JL, Eison MS, Taylor DP, Riblet LA, Temple DJ (1986) Synthesis and biological evaluation of 1-(1,2-benzisothiazol-3-yl)- and (1,2-benzisoxazol-3-yl)piperazine derivatives as potential antipsychotic agents. J Med Chem 29: 359–369Google Scholar
  26. Zushi Y, Harada T, Ujike H, Okumura K (1990) Pharmacological profile of σ receptors labeled by [3H]Haloperidol for the involvement of antipsychotic and neuroprotective effects (in Japanese). Seisin-Yakuryou-Kikin 22: 255–262Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • K. Okumura
    • 1
  • H. Ujike
    • 1
  • K. Akiyama
    • 1
  • S. Kuroda
    • 1
  1. 1.Department of NeuropsychiatryOkayama University Medical SchoolOkayamaJapan

Personalised recommendations