S 16924 ((r)-2-{1-[2-(2,3-dihydro-benzo[1,4] dioxin-5-yloxy)-ethyl]-pyrrolidin-3yl}-1-(4-Fluoro-Phenyl)-Ethanone), a Novel, Potential Antipsychotic with Marked Serotonin (5-HT)1A Agonist Properties: I. Receptorial and Neurochemical Profile in Comparison with Clozapine and Haloperidol

Journal of Pharmacology and Experimental Therapeutics

Volumn 286, Issue 3, 1998, Pages 1341-1355

  Millan, Mark J ^a   Gobert, Alain ^a   Newman Tancredi, Adrian ^a   Audinot, Valérie ^a   Lejeune, Françoise ^a   Rivet, Jean Michel ^a   Cussac, Didier ^a   Nicolas, Jean Paul ^a   Muller, Oliver ^a   Lavielle, Gilbert ^a  

^a INSTITUT DE RECHERCHES INTERNATIONALES SERVIER   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA [1 [2 (1,4 BENZODIOXAN 5 YLOXY)ETHYL] 3 PYRROLIDINYL] 4 FLUOROACETOPHENONE; CLOZAPINE; DOPAMINE; DOPAMINE RECEPTOR; GUANOSINE 5' O (3 THIOTRIPHOSPHATE); HALOPERIDOL; NEUROLEPTIC AGENT; PYRROLIDINE DERIVATIVE; SEROTONIN; SEROTONIN 1 RECEPTOR; SEROTONIN AGONIST; SEROTONIN RECEPTOR; 2 [1 [2 [2,3 DIHYDROBENZO[1,4]DIOXIN 5 YLOXY]ETHYL]PYRROLIDIN 3 YL] 1 (4 FLUOROPHENYL)ETHANONE; ADRENERGIC RECEPTOR; APOMORPHINE; DOPAMINE 2 RECEPTOR; DOPAMINE 3 RECEPTOR; DOPAMINE 4 RECEPTOR; DOPAMINE RECEPTOR STIMULATING AGENT; N [2 [4 (2 METHOXYPHENYL) 1 PIPERAZINYL]ETHYL] N (2 PYRIDYL)CYCLOHEXANECARBOXAMIDE; NORADRENALIN; SEROTONIN 1A ANTAGONIST; SEROTONIN 1A RECEPTOR; SEROTONIN 2A RECEPTOR; SEROTONIN 2C RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL; ARTICLE; CHO CELL; COMPARATIVE STUDY; DRUG EFFECT; HAMSTER; HUMAN; MALE; METABOLISM; PHYSIOLOGY; RAT; WISTAR RAT; ADRENERGIC TRANSMISSION; ANIMAL TISSUE; BRAIN REGION; DOPAMINE BRAIN LEVEL; DOPAMINE UPTAKE; DOPAMINERGIC NERVE CELL; DOPAMINERGIC TRANSMISSION; DOSE RESPONSE; DRUG ACTIVITY; DRUG RECEPTOR BINDING; NERVE CELL INHIBITION; NONHUMAN; NORADRENALIN BRAIN LEVEL; PRIORITY JOURNAL; RECEPTOR AFFINITY; RECEPTOR BLOCKING; SCHIZOPHRENIA; SEROTONIN BRAIN LEVEL; SEROTONIN UPTAKE; SEROTONINERGIC NERVE CELL; SEROTONINERGIC TRANSMISSION;

ANIMALS; ANTIPSYCHOTIC AGENTS; CHO CELLS; CLOZAPINE; CRICETINAE; DOPAMINE; GUANOSINE 5'-O-(3-THIOTRIPHOSPHATE); HALOPERIDOL; HUMANS; MALE; PYRROLIDINES; RATS; RATS, WISTAR; RECEPTORS, DOPAMINE; RECEPTORS, SEROTONIN; RECEPTORS, SEROTONIN, 5-HT1; SEROTONIN; SEROTONIN AGONISTS;

EID: 0032161860     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (78)

1. Andreasen NC, Rezai K, Alliger R, Swayze VW, Flaum M, Kirchner P, Cohen G and O'Leary D (1992) Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Arch Gen Psychiatry 49:943-958.
2. Baldessarini RJ, Huston-Lyons D, Campbell A, Marsh E and Cohen BM (1992) Do central antiadrenergic actions contribute to the atypical properties of clozapine? Br J Psychiatry 60:12-16.
3. Bergson C, Mrzljak L, Smiley JF, Pappy M, Levenson R and Goldman-Rakic PS (1995) Regional, cellular, and subcellular variations in the distribution of Dj and D5 dopamine receptors in primate brain. J Neurosci 15:7821-7836.
4. Blanc G, Trovero F, Vezina P, Hervé D, Godeheu AM, Glowinski J and Tassin JP (1994) Blockade of prefronto-cortical aradrenergic receptors prevents locomotor hyperactivity induced by subcortical D-amphetamine injection. Ear J Neurosci 6:293-298.
5. Bristow LJ, Collinson N, Cook GP, Curtis N, Freedman SB, Kulagowski JJ, Leeson PD, Patel S, Ragan CI, Ridgill M, Saywell KL and Tricklebank MD (1997) L-745,870, a subtype selective dopamine D4 receptor antagonist, does not exhibit a neuroleptic-like profile in rodent behavioral tests. J Pharmacol Exp Ther 283: 1256-1263.
6. Brunello N, Masotto C, Steardo L, Markstein R and Racagni G (1995) New insights into the biology of schizophrenia through the mechanism of action of clozapine. Neuropsychopharmacology 13:177-213.
7. 2A receptor mRNAs and binding site densities are differentially altered in schizophrenia. Neuropsychopharmacology 15:442- 455.
8. Canton H, Verrièle L and Millan MJ (1994) Competitive antagonism of serotonin (5-HT)2c and 5-HT2A receptor-mediated phosphoinositide (PI) turnover by clozapine in the rat: A comparison to other antipsychotics. Neurosci Lett 181:65-68. Casey DE (1993) Serotonergic and dopaminergic aspects of neuroleptic-induced extrapyramidal syndromes in nonhuman primates. Psychopharmacology 112:855S59.
9. Coplan JD, Wolk SI and Klein DF (1995) Anxiety and the serotonin receptors, in Psychopharmacology: The Fourth Generation of Progress (Bloom FE and Kupfer DJ eds) pp 1301-1310, Raven Press, Ltd., New York.
10. Cunningham-Owens DC (1996) Adverse effects of antipsychotic agents. Do newer agents offer advantages? Drugs 51:895-930.
11. Foote SL and Aston-Jones GS (1995) Pharmacology and physiology of central noradrenergic systems, in Psychopharmacology: The Fourth Generation of Progress (Bloom FE and Kupfer DJ eds) pp 347-354, Raven Press, Ltd., New York.
12. 2 antagonism in extrapyramidal functions. Br J Psychiatry 160:(Suppl. 17)34-37.
13. 3HJ5-hydroxytryptamine binding to 5-hydroxytryptaminelncmA_nonB receptors in rat hypothalamus? Mol Pharmacol 49:556-559.
14. Gobert A, Lejeune F, Rivet J-M, Audinot V, Newman-Tancredi A and Millan MJ (1995a) Modulation of the activity of central serotoninergic neurons by novel serotonin1A receptor agonists and antagonists: A comparison to adrenergic and dopaminergic neurons in rats. J Pharmacol Exp Ther 273:1032-1046.
15. 3 autoreceptors control synthesis and release in mesolimbic, mesocortical and nigrostriatal pathways. J Pharmacol Exp Ther 275:899-913.
16. Gobert A, Rivet JM, Audinot V, Newman-Tancredi A, Cistarelli L and Millan MJ (1998) Simultaneous quantification of serotonin, dopamine and noradrenaline levels in single frontal cortex dialysates of freely-moving rats reveals a complex pattern of reciprocal auto- and hetero-receptor mediated control of release. Neuroscience 84:413-429.
17. Goldberg TE and Gold JM (1995) Neurocognitive functioning in patients with schizophrenia, in Psychopharmacology: The Fourth Generation of Progress (Bloom FE and Kupfer DJ eds) pp 1245-1257, Raven Press Ltd., New York.
18. Gurevich EV and Joyce JN (1997) Alterations in the cortical serotonergic system in schizophrenia: A postmortem study. Biol Psychiatry 54:225-232.
19. Haddjeri N, de Montigny C and Blier P (1997) Modulation of the firing activity of noradrenergic neurones in the rat locus coeruleus by the 5-hydroxytryptamine system. Br J Pharmacol 120:865-875.
20. 2 dopamine receptors. Br J Pharmacol 121:731-736.
21. Holcomb HH, Cascella NG, Thaker GK, Medoff DR, Dannais RF, Tamminga CA (1996) Functional sites of neuroleptic drug action in the human brain: PET/FDG studies with and without haloperidol. Am J Psychiatry 153:41-49.
22. Jentsch JD, Tran A, Le D, Youngren KD and Roth RH (1997) Subchronic phencyclidine administration reduces mesoprefrontal dopamine utilization and impairs prefrontal cortical-dependent cognition in the rat. Neuropsychopharmacology 17: 92-99.
23. Kahn RS and Davis KL (1995) New developments in dopamine and schizophrenia, in
24. Psychopharmacology: The Fourth Generation of Progress (Bloom FE and Kupfer DJ eds) pp 1215-1228, Raven Press, Ltd., New York.
25. Kane JM and Freeman HL (1994) Towards more effective antipsychotic treatment. Br J Psychiatry 165:22-31.
26. Kelland MD and Chiodo LA (1996) Serotoninergic modulation of midbrain dopamine systems, in The Modulation of Dopaminergic Neurotransmission by other Ne'irotransmitters (Ashby CR Jr ed) pp 87-122, CRC Press, Boca Raton, FL.
27. Kennett GA, Wood MD, Bright F, Trail B, Riley G, Holland V, Avenell KY, Stean T, Upton N, Bromidge S, Forbes IT, Brown AM, Midlemiss DN and Blackburn TP (1997) SB 242,084, a selective and brain penetrant 5-HT2C receptor antagonist. Neuropharmacology 36:609-620.
28. Kinon BJ and Lieberman JA (1996) Mechanisms of action of atypical antipsychotic drugs: A critical analysis. Psychopharmacology 124:2-34.
29. Knable MB and Weinberger DR (1997) Dopamine, the prefrontal cortex and schizophrenia. J Psychopharmacology 11:123-131.
30. 3 receptor mutant mice. J Neurosci 18:2231-2238.
31. Krämer MS, Last B, Gestson A, Reines SA and the D4 Dopamine Antagonist Group (1997) The effects of a selective D4 dopamine receptor antagonist (L-745,870) in acutely psychotic inpatients with schizophrenia. Arch Gen Psychiatry 54:567-672.
32. Lane RF, Blaha CD and Rivet J-M (1988) Selective inhibition of mesolimbic dcpamine release following chronic administration of clozapine: Involvement of ar adrenergic receptors demonstrated by in vivo voltammetry. Brain Res 460:398401.
33. 1A receptors. Eur J Pharmacol 260:79-83.
34. 1A receptors and their modulation of the activity of Serotoninergic and dopaminergic neurones in the rat. J Pharmacol Exp Ther 280:1241-1249.
35. 3 dopamine receptor: Neurobiology and potential clinical relevance. Pharmacol Rev 49:231-252.
36. Liu ZC and Uetrecht JP (1995) Clozapine is oxidized by activated human neutrophils to a reactive nitrenium ion that irreversibly binds to the cells. J Pharmacol Exp Ther 275:1476-1483.
37. Lovenberg TW, Baron BM, de Lecea L, Miller JD, Prosser RA, Rea MA, Foye JD, Racke M, Slone AL, Siegel BW, Danielson PE, Sutcliffe JG and Erlander MG (1993) A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms. Neuron 11:449-458.
38. 2A/C antagonist, reverse haloperidol-induced catalepsy in rats independently of striatal dopamine release. Psychopharmacology 131:57-63.
39. Maas JW, Contreras SA, Miller AL, Berman N, Bowden CL, Javors MA, Selesch] E and Weintraub S (1993) Studies of catecholamine metabolism in schizophrenia/ psychosis-I. Neuropsychopharmacology 8:97-109.
40. 3H]raclopride is increased in schizophrenia. Biol Psychiai ry 42:648-654.
41. Meador-Woodruff JH, Damask BS, Wang J, Haroutunian V, Davis KL and Watson SJ (1996) Dopamine receptor mRNA expression in human striatum and neocortex. Neuropsychopharmacology 15:17-29.
42. Meiler E, Goldstein M and Bohmaker K (1990) Receptor reserve for 5-hydroxytryptamine1A-mediated inhibition of serotonin synthesis: Possible relationship to anxiolytic properties of 5-hydroxytryptamine1A agonists. Mol Pharmacol 37:231237.
43. Meltzer HY (1995) Atypical antipsychotic drugs, in Psychopharmacology: The Fourth Generation of Progress (Bloom FE and Kupfer DJ eds) pp 1277-1286, Raven Press Ltd., New York.
44. α2A-adrenergic receptors in relation to modulation of cortical monoamine release and potential antidepressant properties. J Pharmacol Er,p Ther 282:132-147.
45. 2 receptors elicits prolactin secretion and catalepsy. J Pharmacol Exp Ther 275:885-898.
46. lc/2 antagonists as therapeutic agents. Drug News Perspect 5:397-406.
47. Moghaddam B and Bunney BS (1990) Differential effects of typical and atypical antipsychotic drugs on the release of dopamine from prefrontal cortex, nuclei] s accumbens and striatum of the rat: An in vivo microdialysis study. J Neurochem 54:1755-1760.
48. Monsma FJ, Shen Y, Ward RP, Hamblin MW and Sibley DA (1993) Cloning and expression of a novel serotonin receptor with high affinity for tricyclic psychotropic drugs. Mol Pharmacol 43:320-327.
49. 4 gene in post-mortem frontal cortex from control and schizophrenics. Neurosci Lett 219: 163-166.
50. Newman-Tancredi A, Audinot V, Chaput C, Verrièle L and Millan MJ (1997) [35S]guanosine-5′-0-(3-thio)triphosphate binding as a measure of efficacy at human
51. 4.4 receptors: Actions of antiparkinsonian and antipsychotic agents. J Pharmacol Exp Ther 282:181-191.
52. 1A receptors. Neuropharmacology 35: 119-121.
53. 2 receptor is antagonized by R( - )-n-propylnorapomorphine, raclopride and phenoxybenzamine. Neuropsychopharmacology 15:5461.
54. Pessia M, Jiang ZG, North RA and Johnson SW (1994) Actions of 5-hydroxytryptamine on ventral tegmental area neurons of the rat in vitro. Brain Res 654:324330.
55. Prinssen EPM, Ellenbroek BA and Cools AR (1994) Combined antagonism of adrenoceptors and dopamine and 5-HT receptors underlies the atypical profile of clozapine. Eur J Pharmacol 262:167-170.
56. 1A receptor activation. Eur J Pharmacol 338:R3-R5.
57. 4 dopamine receptor binding affinity does not distinguish between typical and atypical antipsychotic drugs. Psychopharmacology 120:365-368.
58. Roth BL and Meltzer HY (1995) The role of serotonin in schizophrenia, in Psychopharmacology: The Fourth Generation of Progress (Bloom FE and Kupfer DJ eds) pp 1215-1228, Raven Press, Ltd., New York.
59. Roth BL, Craigo SC, Choudary MS, Uluer A, Monsma FJ, Shen Y, Meltzer HY and Sibley DR ( 1994) Binding of typical and atypical antipsychotic agents to 5-Hydroxytryptamine-6 and 5-Hydroxytryptamine-7 receptors. J Pharmacol Exp Ther 268:1403-1410.
60. Schmidt CJ and Fadayel GM (1995) The selective 5-HT2A receptor antagonist, MDL 100,907, increases dopamine efflux in the prefrontal cortex of the rat. Eur J Pharmacol 273:273-279.
61. Seeman P, Corbett R and Van Toi HM (1997) Atypical neuroleptics have low affinity
62. 4 receptors. Neuropsychopharma-
63. cology 16:93-135. Simpson MDC, Lubman DI, Slater P and Deakin JFW (1996) Autoradiography with
64. 1A receptors in ventral prefrontal cortex
65. in schizophrenia. Biol Psychiatry 39:919-928. Sleight AJ, Boess FG, Bourson A, Sibley DR and Monsma FJ (1997) 5-HT6 and 5-HT7
66. receptors may have clinical potential and the development of selective compounds
67. to examine these possibilities is highly desirable. Drugs News Perspect 10:214 -
68. 224. Sunahara RK, Guan HC, O'Dowd BF, Seeman P, Laurier LG, Ng G, George SR,
69. Torchia J, Van Toi HHM and Niznik HB (1991) Cloning of the gene for a human
70. 350:614-619. Svensson TH, Mathé JM, Andersson JL, Nomikos GG, Hildebrand BE and Marcus M
71. 1-adrenoceptor antagonism.
72. J Clin Psychopharmacology 15:11S-18S. Tallman JF (1997) NGD 94-1; a specific dopamine-4-receptor antagonist. Adv Phar-
73. macol 42:490-492. Tecott LH, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman MF and Jullius
74. 2c serotonin receptors.
75. 2
76. m vivo. J Neurosci 17:2519-2530. Wadenberg M-L (1996) Serotoninergic mechanisms in neuroleptic-induced catalepsy
77. in the rat. Neurosci Biobehau Rev 20:325-339.
78. Send reprint requests to: Dr. Mark J. Millan, Institut de Recherches Servier, Centre de Recherches de Croissy, Psychopharmacology Department, 125 Chemin de Ronde, 78290-Croissy-sur-Seine, Paris, France.