Development of novel, potent, and selective dopamine reuptake inhibitors through alteration of the piperazine ring of 1-[2-(diphenylmethoxy)ethyl]- and 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazines (GBR 12935 and GBR 12909)

Journal of Medicinal Chemistry

Volumn 39, Issue 24, 1996, Pages 4704-4716

  Matecka, Dorota ^a   Rothman, Richard B ^b   Radesca, Lilian ^a   De Costa, Brian R ^a   Dersch, Christina M ^b   Partilla, John S ^b   Pert, Agu ^c   Glowa, John R ^a   Wojnicki, Francis H E ^a   Rice, Kenner C ^a  

^a NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

^c NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COCAINE; DOPAMINE RECEPTOR BLOCKING AGENT; DOPAMINE UPTAKE INHIBITOR; GBR 12395; UNCLASSIFIED DRUG; VANOXERINE;

ANIMAL CELL; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BINDING SITE; CONTROLLED STUDY; DOPAMINE RECEPTOR BLOCKING; DRUG DEPENDENCE TREATMENT; DRUG POTENCY; DRUG SYNTHESIS; ENANTIOMER; INHIBITION KINETICS; INTRAPERITONEAL DRUG ADMINISTRATION; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; CARRIER PROTEINS; COCAINE; DOPAMINE; DOPAMINE PLASMA MEMBRANE TRANSPORT PROTEINS; DOPAMINE UPTAKE INHIBITORS; DRUG DESIGN; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; MEMBRANE GLYCOPROTEINS; MEMBRANE TRANSPORT PROTEINS; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; NERVE TISSUE PROTEINS; PIPERAZINES; RATS; RECEPTORS, DRUG; SEROTONIN; SUBSTANCE-RELATED DISORDERS;

EID: 0030473215     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm960305h     Document Type: Article

References (65)

1. Johanson, C.-E.; Fischman, M. W. The Pharmacology of Cocaine Related to its Abuse. Pharmacol. Rev. 1989, 41, 3-52.
2. Benowitz, N. L. Clinical Pharmacology and Toxicology of Co-caine. Pharmacol. Toxicol. 1993, 72, 3-12.
3. Das, G. Cocaine Abuse in North America: A Milestone in History. J. Clin. Pharmacol. 1993, 33, 296-310.
4. Musto, D. F. Opium, Cocaine and Marijuana in American History. Sci. Am. 1991, 265, 40-47.
5. Warner, E. A. Cocaine Abuse. Ann. Intern. Med. 1993, 119, 226-235.
6. Tims, F. M.; Leukefeld, C. G. Treatment of Cocaine Abusers: Issues and Perspectives. In Cocaine Treatment: Research and Clinical Perspectives; Tims, F. M., Leukefeld, C. G., Eds.; U.S. Department of Health and Human Services: Washington, DC, 1993; pp 1-14.
7. Carroll, F. I.; Lewin, A. H.; Boja, J. W.; Kuhar, M. J. Cocaine Receptor: Biochemical Characterization and Structure-Activity Relationship Studies of Cocaine Analogues at the Dopamine Transporter. J. Med. Chem. 1992, 35, 969-981.
8. Kuhar, M. J.; Ritz, M. C.; Boja, J. W. The Dopamine Hypothesis of the Reinforcing Properties of Cocaine. Trends Neurosci. 1991, 14, 299-302.
9. Ritz, M. C.; Lamb, R. J.; Goldberg, S. R.; Kuhar, M. J. Cocaine Receptors on Dopamine Transporters Are Related to Self-Administration of Cocaine. Science 1987, 237, 1219-1223.
10. Wise, R. A. Catecholamine Theories of Reward: A Critical Review. Brain Res. 1978, 152, 215-247.
11. Carroll, F. I.; Lewin, A. H.; Boja, J. W.; Kuhar, M. J. 3β-(Substituted phenyl)tropan-2-carboxylic Acid Ester Analogues of Cocaine. Synthesis and Biochemical, and Pharmacological Properties. In Drug Design for Neuroscience; Kozikowski, A. P., Ed.; Raven Press: New York, 1993; pp 149-166.
12. Rothman, R. B.; Glowa, J. R. A Review of the Effects of Dopaminergic Agents on Humans, Animals, and Drug-Seeking Behavior, and Its Implications for Medication Development. Mol. Neurobiol. 1995, 10, 1-19.
13. Wise, R. A.; Bozarth, M. A. A Psychomotor Stimulant Theory of Addiction. Pharmacol. Rev. 1987, 94, 469-492.
14. Carroll, F. I.; Lewin, A. H.; Biswas, J. Chemical Approaches to the Treatment of Cocaine Abuse. Pharm. News 1994, 1, 11-16.
15. Mello, N. K.; Mendelson, J. H.; Bree, M. P.; Lucas, S. E. Buprenorphine Suppresses Cocaine Self-Administration by Rhesus Monkeys. Science 1989, 245, 859-862.
16. Meyer, R. E. New Pharmacotherapies for Cocaine Dependence-Revisited. Arch. Gen. Psychiatry 1992, 49, 900-904.
17. Johnson, D. N.; Vocci, F. J. Medications Development at the National Institute on Drug Abuse: Focus on Cocaine. In Cocaine Treatment: Research and Clinical Perspectives; Tims, F. M., Leukefeld, C. G., Eds.; U.S. Department of Health and Human Service: Washington, DC, 1993; pp 57-70.
18. Reid, L. D.; Glick, S. D.; Menkens, K. A.; French, E. D.; Bilsky, E. J.; Porreca, F. Cocaine Self-Administration and Naltrindole, a Delta-Selective Opioid Antagonist. NeuroReport 1995, 6, 1281-1284.
19. Witkin, J. M. Pharmacotherapy of Cocaine Abuse: Preclinical Development. Neurosci. Biobehav. Rev. 1994, 18, 121-142.
20. Winger, G.; Skjoldager, P.; Woods, J. H. Effects of Buprenorphine and Other Opioid Agonists and Antagonists on Alfentanil- and Cocaine-Reinforced Responding in Rhesus Monkeys. J. Pharm. Exp. Ther. 1992, 261, 311-317.
21. Koob, G. F.; Hoang, T. L.; Creese, I. The D1 Dopamine Receptor Antagonist SCH 23390 Increases Cocaine Self-Administration in the Rat. Neurosci. Lett. 1987, 79, 315-320.
22. Katz, J. L.; Witkin, J. M. Behavioral Effects of Cocaine Alone and in Combination with Selective Dopamine Antagonists in the Squirrel Monkey. Psychopharmacology 1991, 103, 33-40.
23. Preston, K. L.; Sullivan, J. T.; Strain, E. C.; Bigelow, G. E. Effects of Cocaine Alone and in Combination with Bromocriptine in Human Cocaine Abusers. J. Pharmacol. Exp. Ther. 1992, 262, 279-291.
24. Rothman, R. B. A Review of the Effects of Dopaminergic Agents in Humans: Implications for Medication Development. NIDA Res. Monogr. 1994, 145, 67-87.
25. 3H]Mazindol Binding Associated with Neuronal Dopamine and Norepinephrine Uptakes Sites. Mol. Pharmacol. 1984, 26, 35-44.
26. 3H]Dopamine Uptake. Eur. J. Pharmacol. 1985, 108, 187-191.
27. He, X.-S.; Raymon, L. P.; Mattson, M. V.; Eldefrawi, M. E.; de Costa, B. R. Further Studies of the Structure-Activity Relationships of 1-[1-(2-Benzo[b]thienyl)cyclohexyl]piperidine. Synthesis and Evaluation of 1-(2-Benzo[6]thienyl)-N,N-dialkylcyclohexy-lamines at Dopamine Uptake and Phencyclidine Binding Sites. J. Med. Chem. 1993, 36, 4075-4081.
28. Newman, A. H.; Kline, R. H.; Allen, A. C.; Izenwasser, S.; George, C.; Katz, J. L. Novel 4′-Substituted and 4,4′-Disubstituted 3α-(Diphenylmethoxy)tropane Analogs as Potent and Selective Dopamine Uptake Inhibitors. J. Med. Chem. 1995, 38, 3933-3940.
29. Meltzer, P. C.; Liang, A. Y.; Madras, B. K 2-Carbomethoxy-3-(diarylmethoxy)-1αH, 5αH-tropane Analogs: Synthesis and Inhibition of Binding at the Dopamine Transporter and Comparison with Piperazines of the GBR Series. J. Med. Chem. 1996, 39, 371-379.
30. 3H]GBR 12935 Binding In vitro to Rat Striatal Membranes: Labeling of the Dopamine Uptake Complex. J. Neurochem. 1987, 48, 1887-1896.
31. Andersen, P. H. The Dopamine Uptake Inhibitor GBR 12909: Selectivity and Molecular Mechanism of Action. Eur. J. Pharmacol. 1989, 166, 493-504.
32. Van der Zee, P.; Roger, H. S.; Goojtes, J.; Hespe, W. Aryl 1,4-Dialk(en)ylpiperazines as Selective and Very Potent Inhibitors of Dopamine Uptake. Eur. J. Med. Chem. 1980, 15, 363-370.
33. Rothman, B. R.; Mele, A.; Reid, A. A.; Akunne, H.; Greig, N.; Thurkauf, A.; Rice, K. C.; Pert, A. Tight Binding Dopamine Inhibitors as Cocaine Antagonists. A Strategy for Drug Development. FEBS Lett. 1989, 257, 341-344.
34. Rothman, R. B. High Affinity Dopamine Reuptake Inhibitors as Potential Cocaine Antagonists: A Strategy for Drug Development. Life Sci. 1990, 46, PL217-PL221.
35. Rothman, R. B.; Mele, A.; Reid, A. A.; Akunne, H. C.; Greig, N.; Thurkauf, A.; de Costa, B. R.; Rice, K. C.; Pert, A. GBR 12909 Antagonizes the Ability of Cocaine to Elevate Extracellular Levels of Dopamine. Pharmacol. Biochem. Behav. 1991, 40, 387-397.
36. Baumann, M. H.; Char, G. U.; de Costa, B. R.; Rice, K. C.; Rothman, R. B. GBR 12909 Attenuates Cocaine-Induced Activation of Mesolimbic Dopamine Neurons in the Rat. J. Pharm. Exp. Ther. 1994, 271, 1216-1222.
37. Glowa, J. R.; Wojnicki, F. H. E.; Matecka, D.; Bacher, J. D.; Mansbach, R. S.; Balster, R. L.; Rice, K. C. Effects of Dopamine Reuptake Inhibitors on Food- and Cocaine-Maintained Responding: I. Dependence on Unit Dose of Cocaine. Exp. Clin. Psychopharmacol. 1995, 3, 219-231.
38. Glowa, J. R.; Wojnicki, F. H. E.; Matecka, D.; Rice, K. C.; Rothman, R. B. Effects of Dopamine Reuptake Inhibitors on Food- and Cocaine-Maintained Responding: II. Comparisons with Other Drugs and Repeated Administrations. Exp. Clin. Psychopharmacol. 1995, 3, 232-239.
39. Rothman, R. B.; Grieg, N.; Kim, A.; de Costa, B. R.; Rice, K. C.; Carroll, F. I.; Pert, A. Cocaine and GBR 12909 Produce Equivalent Motoric Responses at Different Occupancy of the Dopamine Transporter. Pharmacol. Biochem. Behav. 1992, 43, 1135-1142.
40. Sogaard, U.; Michalow, J.; Butler, B.; Laursen, A. L.; Ingersen, S. H.; Skrumsager, B. K.; Rafaelsen, O. J. A Tolerance Study of Single and Multiple Dosing of the Selective Dopamine Inhibitor GBR 12909 in Healthy Subjects. Int. Clin. Psychopharmacol. 1990, 5, 237-251.
41. Foulon, C.; Carreau, L.; Chalon, S.; Desplanches, G.; Frangin, Y.; Besnard, J.-C.; Baulieu, J. L.; Guilloteau, D. Synthesis and In vitro Binding Properties of Halogenated Analogues of GBR as New Dopamine Uptake Carrier Ligands. Nucl. Med. Biol. 1992, 19, 597-600.
42. Deutsch, H. M.; Schweri, M. M.; Culbertson, C. T.; Zalkow, L. H. Synthesis and Pharmacology of Irreversible Affinity Labels as Potential Cocaine Antagonists: Aryl 1,4-Dialkylpiperazines Related to GBR 12783. Eur. J. Pharm. 1992, 220, 173-180.
43. Dutta, A. K.; Meltzer, P. C.; Madras, B. K. Positional Importance of the Nitrogen Atom in Novel Piperidine Analogs of GBR 12909: Affinity and Selectivity for the Dopamine Transporter. Med. Chem. Res. 1993, 3, 209-222.
44. Dutta, A. K.; Xu, C.; Reith, M. E. A. Structure-Activity Relationship Studies of Novel 4-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-1-(3-phenylpropyl)piperidine Analogs: Synthesis and Biological Evaluation at the Dopamine and Serotonin Transporter Sites. J. Med. Chem. 1996, 39, 749-756.
45. Rothman, R. B.; Lewis, B.; Dersch, C. M.; Xu, H.; Radesca, L.; de Costa, B. R.; Rice, K. C.; Kilburn, R. B.; Akunne, H. C.; Pert, A. Identification of a GBR 12935 Homolog, LR 1111, Which is Over 4,000-fold Selective for the Dopamine Transporter, Relative to Serotonin and Norepinephrine Transporters. Synapse 1993, 14, 34-39.
46. Matecka, D.; Radesca, L.; de Costa, B.; Rothman, R. B.; Dersch, C.; Akunne, H.; Lewis, B.; Partilla, J.; Xu, H.; Pert, A.; Rice, K. C. Synthesis, Receptor Binding and Behavioral Studies of N-(2-Diphenylmethoxyethyl)-N′-(3-phenylpropyl)homopiperazine, a Novel GBR 12935 Analog). NIDA Res. Monogr. 1993, 132, 381.
47. Matecka, D.; Rice, K. C.; Rothman, R. B.; de Costa, B. R.; Glowa, J. R.; Wojnicki, F. H.; Pert, A.; George, C.; Carroll, F. I.; Silverthorn, M. L.; Dersch, C. M.; Becketts, K. M.; Partilla, J. S. Synthesis and Absolute Configuration of Chiral Piperazines Related to GBR 12909 as Dopamine Reuptake Inhibitors. Med. Chem. Res. 1995, 5, 43-53.
48. Bonnet, J.-J.; Costentin, J. GBR 12783, a Potent and Selective Inhibitor of Dopamine Uptake: Biochemical Studies In vivo and Ex vivo. Eur. J. Pharmacol. 1986, 121, 199-209.
49. Ariens, E. J. Stereochemistry: A Source of Problems in Medicinal Chemistry. Med. Res. Rev. 1986, 6, 451-466.
50. 3H](+)-PPP to σ Receptors in Rat Brain. Life Sci. 1990, 47, PL133-PL137.
51. 3H]-BTCP}: A Selective Probe for the Dopamine-Reuptake Complex. J. Labelled Comp. Radiopharm. 1991, 29, 165-173.
52. Sharkey, J.; Glen, K. A.; Wolfe, S.; Kuhar, M. J. Cocaine Binding at a Receptors. Eur. J. Pharmacol. 1988, 149, 171-174.
53. Menkel, M.; Terry, P.; Pontecorvo, M.; Katz, J.; Witkin, J. M. Selective σ Ligands Block Stimulant Effects of Cocaine. Eur. J. Pharmacol. 1991, 201, 251-252.
54. Witkin, J. M.; Terry, P.; Menkel, M.; Hickey, P.; Pontecorvo, M.; Ferkany, J.; Katz, J. L. Effects of the Selective σ Receptors Ligand, 6-[6-(4-Hydroxypiperidinyl)hexyloxy]-3-methylflavone (NPC 16377), on Behavioral and Toxic Effects of Cocaine. J. Pharm. Exp. Ther. 1993, 266, 473-482.
55. Tam, S. W. Potential Therapeutic Application of σ Receptor Antagonists. In a Receptors; Itzhak, Y., Ed.; Academic Press Inc.: San Diego, 1994; pp 191-204.
56. 1 Receptors. Mol. Neuropharmaeol. 1993, 3, 117-126.
57. de Costa, B. R.; He, X. Structure-Activity Relationships and Evolution of a Receptor Ligands (1976-present). In a Receptors; Itzhak, Y., Ed.; Academic Press Inc.: San Diego, 1994; pp 45-111.
58. 3H]DA-Uptake-Inhibition to Transporter-Binding-Inhibition Ratios for the In vitro Evaluation of Putative Cocaine Antagonists. Life Sci. 1993, 53, PL267-PL272.
59. Windridge, G. C.; Jorgensen, E. C. 1-Hydroxybenzotriazole as a Racemization Supressing Reagent for the Incorporation of im-Benzyl-L-histidine into Peptides. J. Am. Chem. Soc. 1971, 93, 6318-6319.
60. 3H]BTCP in Rat Caudate Membranes. J. Pharmacol. Exp. Ther. 1994, 268, 1462-1475.
61. 125I]RTI-SS. J. Pharm. Exp. Ther. 1994, 270, 296-309.
62. 3H]1,3-Di(2-toly])-guanidine of Two High Affinity Binding Sites in Guinea Pig Brain: Evidence for Allosteric Regulation by Calcium Channel Antagonists and Pseudoallosteric Modulation by σ Ligands. Mol. Pharmacol. 1991, 39, 222-232.
63. Rodbard, D.; Lenox, R. H.; Wray, H. L.; Ramseth, D. Statistical Characterization of the Random Errors in the Radioimmunoassay Dose-Response Variable. Clin. Chem. 1976, 22, 350-358.
64. Knott, G. D.; Reece, D. K. In Online 1972 International Conference, 1972; pp 497-526.
65. 3H]-(+)-Pentazocine in Guinea Pig Brain. NIDA Res. Monogr. 1993, 132, 404.