The discovery of potent and selective dopamine D4 receptor antagonists

Current Opinion in Chemical Biology

Volumn 2, Issue 4, 1998, Pages 535-540

  Faraci, W Stephen ^a   Zorn, Stevin H ^a   Sanner, Mark A ^a   Fliri, Anton ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLOZAPINE; DOPAMINE 2 RECEPTOR; DOPAMINE 4 RECEPTOR; DOPAMINE RECEPTOR BLOCKING AGENT; DRD4 PROTEIN, HUMAN; NEUROLEPTIC AGENT;

ANIMAL; CHEMISTRY; DRUG ANTAGONISM; DRUG SCREENING; HUMAN; REVIEW;

ANIMALS; ANTIPSYCHOTIC AGENTS; CLOZAPINE; DOPAMINE ANTAGONISTS; DRUG EVALUATION, PRECLINICAL; HUMANS; RECEPTORS, DOPAMINE D2; RECEPTORS, DOPAMINE D4;

EID: 0032133303     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1367-5931(98)80131-2     Document Type: Article

References (27)

1. Van Toi HHM, Bunzow JR, Guan H-C, Sunahara RK, Seeman P, Niznik HB, Civelli O: Cloning of a human dopamine D4 receptor gene with high affinity for the antipsychotic clozapine. Nature 1991, 358:149-152.
2. Seeman P, Guan H-C, Van Tol HHM: Dopamine D4 receptors are elevated in schizophrenia. Nature 1993, 365:441-445.
3. Murray AM, Hyde TM, Knable MB, Herman MM, Bigelow LB, Carter JM, Weinberger DR, Kleinman J: Distribution of putative D4 dopamine receptors in postmortem striatum from patients with schizophrenia. J Neurosci 1995, 15:2186-2191.
4. Sumiyoshi T, Stockmeier CA, Overholser JC, Thompson PA, Meltzer TA: Dopamine D4 receptors and effects of guanine nucleotides on [3H]raclopride binding in postmortem caudate nucleus of subjects with schizophrenia or major depression. Brain Res 1995, 681:109-116.
5. Reynolds GP, Mason SL: Absence of detectable striatal dopamine D4 receptors in drug-treated schizophrenia. Eur J Pharmacol 1995, 281:R5-R6.
6. Seeman P: Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4. Neuropsychopharmacology 1992, 7:261-284.
7. Kulagowski JJ, Patel S: Dopamine D4 receptor antagonists. Curr Pharm Design 1997, 3:355-366.
8. Sanner MA: Selective dopamine D4 receptor antagonists. Exp Opin Ther Patents 1998, 8:383-393. This review outlines recent activity in the discovery and development of D4 receptor antagonists by a number of pharmaceutical and biotechnology companies. The focus is on the different chemotypes identified and the potency and selectivity of each.
9. Sanner MA, Chappie TA, Dunaiskis AR, Fliri AF, Desai KA, Zorn SH, Jackson ER, Johnson CG, Morrone JM, Seymour PA et al.: Synthesis, SAR and pharmacology of CP-293,019: a potent, selective dopamine D4 receptor antagonist. Bioorg Med Chem Lett 1998, 8:725-730.
10. Zorn SH, Johnson CG, Jackson ER, Seymour P, Majchrzak M, Mansbach R, Winston E, de Wet JR, Dunaiskis A, Chappie TA, Sanner MA: CP-293,019: a D4 dopamine antagonist with an in vitro and in vivo profile suggestive of an atypical antipsychotic. Soc Neurosci Abstr 1996, 22:1771.
11. Majchrzak M, Zorn SH, Sanner MA, Seymour P: Blockade of the locomotor activity response to apomorphine: a proposed in vivo behavioral assay to detect D4 receptor antagonists. Soc Neurosci Abstr 1997, 23:413.
12. Mansbach RS, Brooks EW, Sanner MA, Zorn SH: Selective dopamine D4 receptor antagonists reverse apomorphine-induced blockade of prepulse inhibition. Psychopharmacology (Berlin) 1998, 135:194-200. Data in this paper show that three structurally distinct, selective D4 receptor antagonists are active in an animal model that has previously detected clinically effective antipsychotic drugs.
13. Okuyama S, Chaki S, Kawashima N: The atypical antipsychotic profile of NRA0045, a novel dopamine D4 and 5-hydroxytryptamine 2A receptor antagonist, in rats. Br J Pharmacol 1997, 121:515-525.
14. Merchant KM, Gill GS, Harris DW, Huff RM, Eaton MJ, Lookingland K, Lutzke BS, McCall RB, Piercey MF, Schreur PJKD et al.: Pharmacological characterization of U-101387, a dopamine D4 receptor selective antagonist. J Pharmacol Exp Ther 1996, 279:1392-1403.
15. Bristow LJ, Collinson N, Cook GP, Curtis N, Freedman SB, Kulagowski JJ, Leeson PD, Patel S, Ragan CI, Ridgill M et al.: 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 1997, 283:1256-1263.
16. Millan MJ, Newman-Tancredi A, Audinot V, Brocco M, Gobert A, Rivet JM, Peglion JL: S 18126, novel, potent and selective antagonist at human (h) recombinant dopamine (DA) hD4 receptors. Soc Neurosci Abstr 1996, 22:1772.
17. Niemegeers CJE, Janssen PAJ: A systematic study of the pharmacological activities of dopamine antagonists. Life Sci 1979, 24:2201-2215.
18. Roberts DCS, Zis AP, Fibiger HC: Ascending catecholamine pathways and amphetamine-induced locomotor activity: importance of dopamine and apparent non-involvement of norepinephrine. Brain Res 1975, 93:441-454.
19. Tallman JF, Primus RJ, Brodbeck R et al.: NGD 94-1: identification of a novel, high-affinity antagonist at the human dopamine D4 receptor. J Pharmacol Exp Ther 1997, 282:1011-1019.
20. Braff DL, Stone C, Callaway E, Geyer M, Glick I, Bali L: Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 1978, 15:339-343.
21. Mansbach RS, Geyer MA: Effects of phencyclidine and phencyclidine biologs on sensorimotor gating in the rat. Neuropsychopharmocology 1989, 2:299-308.
22. Mansbach RS, Geyer MA, Braff DL: Dopaminergic stimulation disrupts sensormotor gating in the rat. Psychopharmacology (Berlin) 1988, 94:507-514.
23. Sipes TA, Geyer MA: Multiple serotonin subtypes modulate prepulse inhibition of the startle response in rats. Neuropharmacology 1994, 33:441-448.
24. Holland JP, Costello DG, de Wet JR, Rollema H, Zorn SH, Seeger TF. CP-293,019, a D4-selective dopamine receptor antagonist produces clozapine-like effects on c-fos mRNA and dopamine levels in rat brain. Soc Neurosci Abstr 1996, 22:1771.
25. Robertson GS, Matsumura H, Fibiger HC: Induction patterns of Fos-like immunoreactivity in the forebrain as predictors of atypical antipsychotic activity. J Pharmacol Exp Ther 1994, 271:1058-1066.
26. Patel A, Freedman S, Chapman KL, Emms F, Fletcher AE, Knowles M, Marwood R, McAllister G, Myers J, Patel S et al.: Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor. J Pharmacol Exp Ther 1997, 283:636-647.
27. Bristow LJ, Kramer MS, Kulagowski J, Patel S, Ragan CI, Seabrook GR: Schizophrenia and L-745,870, a novel dopamine D4 receptor antagonist. Trends Pharmacol Sci 1997, 18:186-188. The first clinical study with a D4-receptor-selective compound reported. L-745,870 was tested in a small study at a single fixed dose and found to be ineffective in the treatment of schizophrenia.