Skip to main content
SpringerLink
Log in
Book cover

Neurotransmitter Transporters pp 263–295Cite as

Dopamine Transporter Uptake Blockers

Structure-Activity Relationships

  • Chapter

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

The dopamine transporter (DAT), a protein located on presynaptic nerve terminals (43,44,61), plays a major role in the reuptake of released dopamine. Uptake of DA is sodium- and chloride ion-, as well as temperature- and time-dependent, and is inhibited by a variety of compounds, including cocaine. Even though cocaine binds to several sites in the brain, only binding potencies at the DA site have been shown to correlate with the reinforcing properties of cocaine in animal models, which are the primary factors in its abuse. Thus, the DAT has been called a cocaine receptor (11,81) and may be the initial site responsible for producing cocaine’s drug reinforcement. The cDNA for the DAT has been cloned from rat (39,51,85), bovine (88), and human (91) brains. The hydrophobicity profile indicates 12 possible membrane-spanning regions with the amino and carboxy termini located intracellularly. The protein from human and rat brains contains three and four extracellular N-glycosylation sites, respectively (Fig. 1).

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   74.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Physicians’ Desk Reference,49th ed., Medical Economics Data, Montvale, NJ, 1995, pp. 309, 897.

    Google Scholar 

  2. Physicians’ Desk Reference,49th ed., Medical Economics Data, Montvale, NJ, 1995, pp. 2190–2191, 269.

    Google Scholar 

  3. Abraham, P., Pitner, J. B., Lewin, A. H., Boja, J. W., Kuhar, M. J., and Carroll, F. I. N-Modified analogues of cocaine: synthesis and inhibition of binding to the cocaine receptor. J. Med. Chem. 35 (1992) 141–144.

    Article  PubMed  CAS  Google Scholar 

  4. Aeberli, P., Eden, P., Gogerty, J. H., Houlihan, W. J., and Penberthy, C. 5-Aryl2,3-dihydro-5H-imidazo[2–1-a]isoindol-5-ols. A novel class of anorectic agents. J. Med. Chem. 18 (1975) 177–182.

    Article  PubMed  CAS  Google Scholar 

  5. Aeberli, P., Eden, P., Gogerty, J. H., Houlihan, W. J., and Penberthy, C. Anorectic agents. 2. Structural analogs of 5-(p-chlorophenyl)-2,3-dihydro 5Himdazo[2,1-a]isoindol-5-ol. J. Med. Chem. 18 (1975) 182–185.

    Article  CAS  Google Scholar 

  6. Anderson, P. H. Biochemical and pharmacological characterization of [3H]GBR-12935 binding in vitro to rat striatal membranes: labeling of the dopamine uptake complex. J. Neurochem. 48 (1987) 1887–1896.

    Article  Google Scholar 

  7. Barcza, S. and Houlihan, W. J. Structure determination of the anorexic agent Mazindol. J. Pharm. Sci. 64 (1975) 829–831.

    Article  PubMed  CAS  Google Scholar 

  8. Bennett, B. A., Wichems, C. H., Hollingsworth, C. K., Davies, H. M. L., Thornley, C., Sexton, T., and Childers, S. R. Novel 2-substituted cocaine analogs: uptake and ligand binding studies at dopamine, serotonin and nor-epinephrine transport sites in the rat brain. J. Pharmacol. Exp. Ther. 272 (1995) 1176–1186.

    PubMed  CAS  Google Scholar 

  9. Berger, P., Gawin, F., and Koster, T. R., Treatment of cocaine abuse with mazindol. Lancet II (1989) 283.

    Google Scholar 

  10. Berger, P., Janowsky, A., Vocci, F., Skolnick, P., Schweri, M. M., and Paul, S. M. [3H]GBR-12935: a specific high affinity ligand for labeling the dopamine transport complex. Eur. J. Pharmacol. 107 (1985) 289, 290.

    Google Scholar 

  11. Bergman, J., Madras, B. K., Johnson, S. E., and Spealman, R. D. Effects of cocaine and related drugs in nonhuman primates. III. Self-administration by squirrel monkeys. J. Pharmacol. Exp. Ther. 251 (1989) 150–155.

    PubMed  CAS  Google Scholar 

  12. Boja, J. W., Kuhar, M. J., Kopajtic, T., Yang, E., Abraham, P., Lewin, A. H., and Carroll, F. I. Secondary amine analogues of 313-(4’-substituted phenyl)tropane213-carboxylic acid esters and N-norcocaine exhibit enhanced affinity for serotonin and norepinephrine transporters. J. Med. Chem. 37 (1994) 1220–1223.

    Article  PubMed  CAS  Google Scholar 

  13. Boja, J. W., McNeill, R. M., Lewin, A. H., Abraham, P., Carroll, F. I., and Kuhar, M. J. Selective dopamine transporter inhibition by cocaine analogs. NeuroReport 3 (1992) 984–986.

    CAS  Google Scholar 

  14. Bonnet, J.-J., Protais, P., Chagraoui, A., and Costentin, J. High-affinity [3H]GBR 12783 binding to a specific site associated with the neuronal dopamine uptake complex in the central nervous system. Eur. J. Pharmacol. 126 (1986) 211–222.

    Article  PubMed  CAS  Google Scholar 

  15. Carroll, F. I., Abraham, P., Lewin, A. H., Parham, K. A., Boja, J. W., and Kuhar, M. J. Isopropyl and phenyl esters of 313-(4-substituted phenyl)tropan-2ß-carboxylic acids. Potent and selective compounds for the dopamine transporter. J. Med. Chem. 35 (1992) 2497–2500.

    Article  PubMed  CAS  Google Scholar 

  16. Carroll, F. I. and Lewin, A. H. (1996) (unpublished).

    Google Scholar 

  17. Carroll, F. I., Gao, Y., Abraham, P., Lewin, A. H., Lew, R., Patel, A., Boja, J. W., and Kuhar, M. J. Probes for the cocaine receptor. Potentially irreversible ligands for the dopamine transporter. J. Med. Chem. 35 (1992) 1813–1817.

    CAS  Google Scholar 

  18. Carroll, F. I., Gao, Y., Rahman, M. A., Abraham, P., Lewin, A. H., Boja, J. W., and Kuhar, M. J. Synthesis, ligand binding, QSAR, and CoMFA study of 313(p,substituted phenyl)tropan-23-carboxylic acid methyl esters. J. Med. Chem. 34 (1991) 2719–2927.

    Article  PubMed  CAS  Google Scholar 

  19. Carroll, F. I., Gray, J. L., Abraham, P., Kuzemko, M. A., Lewin, A. H., Boja, J. W., and Kuhar, M. J. 3-Aryl-2-(3’-substituted-1’,2’,4’-oxadiazol-5’-yl)tropane analogues of cocaine: affinities at the cocaine binding site at the dopamine, serotonin, and norepinephrine transporters. J. Med. Chem. 36 (1993) 2886–2890.

    Article  PubMed  CAS  Google Scholar 

  20. Carroll, F. I., Kotian, P., Dehghani, A., Gray, J. L., Kuzemko, M. A., Parham, K. A., Abraham, P., Lewin, A. H., Boja, J. W., and Kuhar, M. J. Cocaine and 3ß-(4’-substituted phenyl)tropane-2ß-carboxylic acid ester and amide analogues. New high-affinity and selective compounds for the dopamine transporter. J. Med. Chem. 38 (1995) 379–388.

    Article  PubMed  CAS  Google Scholar 

  21. Carroll, F. I., Kotian, P., Gray, J. L., Abraham, P., Kuzemko, M. A., Lewin, A. H., Boja, J. W., and Kuhar, M. J. 313-(4’-Chlorophenyl)tropan-213-carboxamides and cocaine amide analogues: new high affinity and selective compounds for the dopamine transporter. Med. Chem. Res. 3 (1993) 468–472.

    Google Scholar 

  22. Carroll, F. I., Kuzemko, M. A., Gao, Y., Abraham, P., Lewin, A. H., Boja, J. W., and Kuhar, M. J. Synthesis and ligand binding of 313-(3-substituted phenyl)-and 3[3-(3,4-disubstituted phenyl)tropane-213-carboxylic acid methyl esters. Med. Chem. Res. 1 (1992) 382–387.

    Google Scholar 

  23. Carroll, F. I., Lewin, A. H., Abraham, P., Parham, K., Boja, J. W., and Kuhar, M. J. Synthesis and ligand binding of cocaine isomers at the cocaine receptor. J. Med. Chem. 34 (1991) 883–886.

    Article  PubMed  CAS  Google Scholar 

  24. Carroll, F. I., Lewin, A. H., Boja, J. W., and Kuhar, M. J. Cocaine receptor: Biochemical characterization and structure-activity relationships for the dopamine transporter. J. Med. Chem. 35 (1992) 969–981.

    Article  PubMed  CAS  Google Scholar 

  25. Carroll, F. I., Mascarella, S. W., Kuzemko, M. A., Gao, Y., Abraham, P., Lewin, A. H., Boja, J. W, and Kuhar, M. J. Synthesis, ligand binding, and QSAR (CoMFA and classical) study of 313-(3’-substituted phenyl)-, 3ß-(4’-substituted phenyl)-, and 3 3-(3’,4’-disubstituted phenyl)tropane-213-carboxylic acid methyl esters. J. Med. Chem. 37 (1994) 2865–2873.

    Article  PubMed  CAS  Google Scholar 

  26. Chait, L. D., Uhlenhuth, E. H., and Johansen, C. E. Reinforcing and subjective effects of several anorectics in normal human volunteers. J. Pharmacol. Exp. Ther. 242 (1987) 777–783.

    PubMed  CAS  Google Scholar 

  27. Clarke, R. L., Daum, S. J., Gambino, A. J., Aceto, M. D., Pearl, J., Levitt, M., Cumiskey, W. R., and Bogado, E. F. Compounds affecting the central nervous system. 4. 313-Phenyltropane-2-carboxylic esters and analogs. J. Med. Chem. 16 (1973) 1260–1267.

    Article  PubMed  CAS  Google Scholar 

  28. Coderc, E., Cerruti, P., Vignon, J., Rouayrenc, J. F., and Kamenka, J.-M.PCP receptor and dopamine uptake sites are discriminated by chiral TCP and BTCP derivatives of opposite configuration. Eur. J. Med. Chem. 30 (1995) 463–470.

    Article  CAS  Google Scholar 

  29. Coderc, E., Martin-Fardon, R., Vignon, J., and Kamenka, J.-M. New compounds resulting from structural and biochemical similarities between GBR 12783 and BTCP, two potent inhibitors of dopamine uptake. Eur. J. Med. Chem—Chim. Thera. 28 (1993) 893–898.

    Article  CAS  Google Scholar 

  30. Colpaert, F. C., Niemegeers, C. J. E., and Janssen, P. A. J. Discriminative stimulus properties of cocaine. Neuropharmacological characteristics as derived from stimulus generalization experiments. Pharmacol. Biochem. Behay.10 (1978) 535–546.

    Google Scholar 

  31. Davies, H. M. L., Saikali, E., Huby, N. J. S., Gilliat, V. J., Matasi, J. J., Sexton, T., and Childers, S. R. Synthesis of 2(3-Acyl-33-aryl-8-azabicyclo[3.2.1]octanes and their binding affinities at dopamine and serotonin transport sites in rat striatum and frontal cortex. J. Med. Chem. 37 (1994) 1262–1268.

    Article  PubMed  CAS  Google Scholar 

  32. Davies, H. M. L., Saikali, E., Sexton, T., and Childers, S. R. Novel 2-substituted cocaine analogs: binding properties at dopamine transport sites in rat striatum. Eur. J. Pharmacol. Mol. Pharmacol. Sec. 244 (1993) 93–97.

    Article  CAS  Google Scholar 

  33. Deutsch, H. M., Schweri, M., M., Culbertson, C. T., and Zalkow, L. H. Synthesis and pharmacology of irreversible affinity labels as potential cocaine antagonists: aryl 1,4-dialkylpiperazines related to GBR-12783. Eur. J. Pharmacol. 220 (1992) 173–180.

    Article  PubMed  CAS  Google Scholar 

  34. Deutsch, H. M. and Schweri, M. M. Can stimulant binding and dopamine transport be differentiated? Studies with GBR 12783 derivatives. Lift Sci 55 (1994) PL 115–120.

    Google Scholar 

  35. Deutsch, H. M., Shi, Q., Kowalik, E., and Schweri, M. M. Synthesis and pharmacology of potential cocaine antagonists. 2. Structure-activity relationship studies of aromatic ring substituted methylphenidate analogs. J. Med. Chem. 39 (1996) 1201–1209.

    Article  PubMed  CAS  Google Scholar 

  36. Elmaleh, D. R., Madras, B. K., Shoup, T. M., Byon, C., Hanson, R. N., Liang, A. Y., Meltzer, P. C., and Fischman, A. J. Radiosynthesis and evaluation of E and Z- PI1–2[3-carbomethoxy-3ß-(4-fluorophenyl)-N-(iodoprop-1-en-3-yl)nortropane (Altropane): a selective SPECT agent for imaging DA reuptake sites. J. Nucl. Chem. in press.

    Google Scholar 

  37. Fahey, M. A., Canfield, D. A., Spealman, R. D., and Madras, B. K. Comparison of [3H]GBR 12935 and [3H]cocaine binding sites in monkey brain. Soc. Neurosci. Abstracts 515 (1989) 252.

    Google Scholar 

  38. Gatley, S. J., Yu, D.-W., Fowler, J. S., MacGregor, R. R., Schlyer, D. J., Dewey, S. L., Wolf, A. P., Martin, T., Shea, C. E., and Volkow, N. D. Studies with differentially labeled [11C]cocaine, [11C]norcocaine, [“C]benzoylecgonine, and [11C]-and 4’-[18F]fluorococaine to probe the extent to which [11C]cocaine metabolites contribute to PET images of the baboon brain. J. Neurochem. 62 (1994) 1154–1162.

    Article  PubMed  CAS  Google Scholar 

  39. Giros, B., el Mestikawy, S., Bertrand, L., and Caron, M. G. Cloning and functional characterization of a cocaine-sensitive dopamine transporter. FEBS Lett. 295 (1991) 149–154.

    Article  PubMed  CAS  Google Scholar 

  40. Giros, B., Wang, Y.-M., Suter, S., McLeskey, S. B., Pifl, C., and Caron, M. G. Delineation of discrete domains for substrate, cocaine, and tricyclic antidepressant interactions using chimeric dopamine-norepinephrine transporters. J. Biol. Chem. 269 (1994) 15,985–15,988.

    Google Scholar 

  41. He, X.-S., Raymon, L. P., Mattson, M. V., Eldefrawi, M. E., and de Costa, B. R. Synthesis and biological evaluation of 1-[1-(2-benzo[b]-thienyl)cyclohexyl]piperidine homologues at dopamine-uptake and phencyclidine-and a-binding sites. J. Med. Chem. 36 (1993) 1188–1193.

    Article  PubMed  CAS  Google Scholar 

  42. He, X.-S., Raymon, L. P., Mattson, M. V., Eldefrawi, M. E., and de Costa, B. R. Further studies of the structure-activity relationships of 1-[1-(2benzo[b]thienyl)cyclohexyl]piperidine. Synthesis and evaluation of 1-(2benzo[b]thienyl)-N,N-dialkylcyclohexylamines at dopamine uptake and phencyclidine binding sites. J. Med. Chem. 36 (1993) 4075–4081.

    Article  PubMed  CAS  Google Scholar 

  43. Horn, A. S. In Roberts, P. J., Woodruff, G. N., and Iversen, L. L. (eds.), Dopamine. Advances in Biochemical Psychopharmacology, vol. 19, Raven, New York, 1978, pp. 25–34.

    Google Scholar 

  44. Horn, A. S. Dopamine uptake: a review of progress in the last decade. Prog. Neurobiol. 34 (1990) 387–400.

    Article  PubMed  CAS  Google Scholar 

  45. Houlihan, W. J., Boja, J. W., Kuhar, M. J., Kopajtic, T. A., and Parrino, V. A. Mazindol analogs as potential inhibitors of the cocaine binding site. Structure activity relationships. Abstracts of College on Problems of Drug Dependence, Scottsdale, AZ, June 10–15, 1995, pp. 66.

    Google Scholar 

  46. Houlihan, W. J., Boja, J. W., Parrino, V. A., Kuhar, M. J., and Kopajtic, T. A. Halogenated mazindol analogs as potential inhibitors of the cocaine binding site at the dopamine transporter. 208th American Chemical Society National Meeting, Abstr. No. 173, Washington, DC, August 21–25, 1994.

    Google Scholar 

  47. Houlihan, W. J., Heikkila, R. E., and Babington, R. G. Pharmacological studies with several analogs of mazindol: correlation between effects on dopamine uptake and various in vivo responses. Eur. J. Pharmacol. 71 (1981) 277–286.

    Article  PubMed  Google Scholar 

  48. Javitch, J. A., Blaustein, R. O., and Snyder, S. H. [ 3 H] Mazindol binding associated with neuronal dopamine and norepinephrine uptake sites. Mol. Pharmacol. 26 (1984) 35–44.

    PubMed  CAS  Google Scholar 

  49. Johnson, K. M., llergmann, J. S., and Kozikowski, A. P. Cocaine and dopamine differentially protect [3H]mazindol binding sites from alkylation by N-ethylmaleimide. Eur. J. Pharmacol. 227 (1992) 411–415.

    Article  PubMed  CAS  Google Scholar 

  50. Kelkar, S. V., Izenwasser, S., Katz, J. L., Klein, C. L., Zhu, N., and Trodell, M. L. Synthesis, cocaine receptor affinity, and dopamine uptake inhibition of several new 213-substituted 313-phenyltropanes. J. Med. Chem. 37 (1994) 3875–3877.

    Article  PubMed  CAS  Google Scholar 

  51. Kilty, J. E., Lorang, D., and Amara, S. G. Cloning and expression of a cocaine-sensitive rat dopamine transporter. Science 254 (1991) 528, 529.

    Google Scholar 

  52. Kitayama, S., Shimada, S., Xu, H., Markham, L., Donovan, D. M., and Uhl, G. R. Dopamine transporter site-directed mutations differentially alter substrate transport and cocaine binding. Proc. Natl. Acad. Sci. USA 89 (1992) 7782–7785.

    Article  PubMed  CAS  Google Scholar 

  53. Kline, R. H., Jr., Wright, J., Fox, K. M., and Eldefrawi, M. E. Synthesis of 3arylecgonine analogues as inhibitors of cocaine binding and dopamine uptake. J. Med. Chem. 33 (1990) 2024–2027.

    Article  PubMed  CAS  Google Scholar 

  54. Kline, R. H., Jr., Wright, J., Eshleman, A. J., Fox, K. M., and Eldefrawi, M. E. Synthesis of 3-carbamoylecgonine methyl ester analogues as inhibitors of cocaine binding and dopamine uptake. J. Med. Chem. 34 (1991) 702–705.

    Article  PubMed  CAS  Google Scholar 

  55. Koek, W., Colpaert, F. C., Woods, J. H., and Kamenka, J.-M. The phencyclidine (PCP) analog N-[1-(2-benzo(B)thiophenyl)cyclohexyl]-piperidine shares cocaine-like but not other characteristic behavioral effects with PCP, ketamine and MK-801. J. Pharmacol. Exp. Ther. 250 (1989) 1019–1027.

    PubMed  CAS  Google Scholar 

  56. Kotian, P., Abraham, P., Lewin, A. H., Mascarella, S. W., Boja, J. W., Kuhar, M. J., and Carroll, F. I. Synthesis and ligand binding study of 3(3-(4’-substituted phenyl)-213-(heterocyclic)tropanes. J. Med. Chem. 38 (1995) 3451–3453.

    Article  PubMed  CAS  Google Scholar 

  57. Kozikowski, A. P., Roberti, M., Xiang, L., Bergmann, J. S., Callahan, P. M., Cunningham, K. A., and Johnson, K. M. Structure-activity relationship studies of cocaine: replacement of the C-2 ester group by vinyl argues against H-bonding and provides an esterase-resistant, high-affinity cocaine analogue. J. Med. Chem. 35 (1992) 4764–4766.

    Article  PubMed  CAS  Google Scholar 

  58. Kozikowski, A. P., Saiah, M. K. E., Bergmann, J. S., and Johnson, K. M. Structure-activity relationship studies of N-sulfonyl analogs of cocaine: role of ionic interaction in cocaine binding. J. Med. Chem. 37 (1994) 3440–3442.

    Article  PubMed  CAS  Google Scholar 

  59. Kozikowski, A. P., Saiah, M. K. E., Johnson, K. M., and Bergmann, J. S. Chemistry and biology of the 2(3-alkyl-3(3-phenyl analogues of cocaine: subnanomolar affinity ligands that suggest a new pharmacophore model at the C2 position. J. Med. Chem. 38 (1995) 3086–3093.

    Article  PubMed  CAS  Google Scholar 

  60. Kozikowski, A. P., Xiang, L., Tanaka, J., Bergmann, J. S., and Johnson, K. M. Use of nitrile oxide cycloaddition (NOC) chemistry in the synthesis of cocaine analogues: mazindol binding and dopamine uptake studies. Med. Chem. Res. 1 (1991) 312–321.

    CAS  Google Scholar 

  61. Kuhar, M. J. Neurotransmitter uptake: a tool in identifying neurotransmitter-specific pathways. Life Sci. 13 (1973) 1623–1634.

    Article  PubMed  CAS  Google Scholar 

  62. Kuhar, M. J., Ritz, M. C., and Boja, J. W. The dopamine hypothesis of the reinforcing properties of cocaine. Trends Neurosci. 14 (1991) 299–302.

    Article  PubMed  CAS  Google Scholar 

  63. Lewin, A. H., Gao, Y., Abraham, P., Boja, J. W., Kuhar, M. J., and Carroll, F. I. 213-Substituted analogues of cocaine. Synthesis and inhibition of binding to the cocaine receptor. J. Med. Chem. 35 (1992) 135–140.

    Article  PubMed  CAS  Google Scholar 

  64. Madras, B. K., Kamien, J. B., Fahey, M. A., Canfield, D. R., Milius, R. A., Saha, J. K., Neumeyer, J. L., and Spealman, R. D. N-Modified fluorophenyltropane analogs of cocaine with high affinity for cocaine receptors. Pharmacol. Biochem. Behay. 35 (1990) 949–953.

    Article  CAS  Google Scholar 

  65. Madras, B. K., Reith, M. E. A., Meltzer, P. C., and Dutta, A. K. 0–526, a piperidine analog of GBR 12909, retains high affinity for the dopamine transporter in monkey caudate-putamen. Eur. J. Pharmacol.-Mol. Pharmacol. Sec. 267 (1993) 167–173.

    Article  Google Scholar 

  66. Madras, B. K., Spealman, R. D., Fahey, M. A., Neumeyer, J. L., Saha, J. K., and Milius, R. A. Cocaine receptors labeled by [3H]2ß-carbomethoxy-30-(4-fluorophenyl)tropane. Mol. Pharmacol. 36 (1989) 518–524.

    PubMed  CAS  Google Scholar 

  67. Matecka, D., Rice, K. C., Rothman, R. B., de Costa, B. R., Glowa, J. R., Wojnicki, F. H., Becketts, K. M., and Partilla, J. S. Synthesis and absolute configuration of chiral piperazines related to GBR 12909 as dopamine uptake inhibitors. Med. Chem. Res. 5 (1994) 43–53.

    Google Scholar 

  68. McElvain, J. S. and Schenk, J. O. A multisubstrate mechanism of striatal dopamine uptake and its inhibition by cocaine. Biochem. Pharmacol. 43 (1992) 2189–2199.

    Article  PubMed  CAS  Google Scholar 

  69. Meltzer, P. C., Liang, A. Y., Brownell, A.-L., Elmaleh, D. R., and Madras, B. K. Substituted 3-phenyltropane analogs of cocaine: synthesis, inhibition of binding at cocaine recognition sites, and positron emission tomography imaging. J. Med. Chem. 36 (1993) 855–862.

    Article  PubMed  CAS  Google Scholar 

  70. Meltzer, P. C., Liang, A. Y., and Madras, B. K. 2-Carbomethoxy-3-(diarylmethoxy)-laH,5aH-tropane analogs: synthesis and inhibition of binding at the dopamine transporter and comparison with piperazines of the GBR series. J. Med. Chem. 39 (1996) 371–379.

    Article  PubMed  CAS  Google Scholar 

  71. Meltzer, P. C., Liang, A. Y., and Madras, B. K. The discovery of an unusually selective and novel cocaine analog: difluoropine. Synthesis and inhibition of binding at cocaine recognition sites. J. Med. Chem. 37 (1994) 2001–2010.

    Article  PubMed  CAS  Google Scholar 

  72. Metwally, S. A. M., Gatley, S. J., Wolf, A. P., and Yu, D.-W. Synthesis and binding to striatal membranes of no carrier added I-123 labeled 4’-iodococaine. J. Label. Compd. Radiopharm. XXXI (1992) 219–225.

    Article  Google Scholar 

  73. Milius, R. A., Saha, J. K., Madras, B. K., and Neumeyer, J. L. Synthesis and receptor binding of N-substituted tropane derivatives. High-affinity ligands for the cocaine receptor. J. Med. Chem. 34 (1991) 1728–1731.

    Article  PubMed  CAS  Google Scholar 

  74. Muller, L., Halldin, C., Farde, L., Karlsson, P., Hall, H., Swahn, C. G., Neumeyer, J., Gao, Y., and Milius, R. [11C]3-CIT, a cocaine analogue. Preparation, autoradiography and preliminary PET investigations. Nucl. Med. Biol. 20 (1993) 249–255.

    Article  PubMed  CAS  Google Scholar 

  75. Neumeyer, J. L., Wang, S., Gao, Y., Milius, R. A., Kula, N. S., Campbell, A., Baldessarini, R. J., Zea-Ponce, Y., Baldwin, R. M., and Innis, R. B. N-coFluoroalkyl analogs of (1R)-2[3-carbomethoxy-3(3-(4-iodophenyl)-tropane (ßCIT): radiotracers for positron emission tomography and single photon emission computed tomography imaging of dopamine transporters. J. Med. Chem. 37 (1994) 1558–1561.

    Article  PubMed  CAS  Google Scholar 

  76. Newman, A. H., Allen, A. C., Izenwasser, S., and Katz, J. L. Novel 3a(diphenylmethoxy)tropane analogs: potent dopamine uptake inhibitors without cocaine-like behavioral profiles. J. Med. Chem. 37 (1994) 2258–2261.

    Article  PubMed  CAS  Google Scholar 

  77. Newman, A. H., Kline, R. H., Allen, A. C., Izenwasser, S., George, C., and Katz, J. L. Novel 4’- and 4’,4“-substituted-3a-(diphenylmethoxy)tropane analogs are potent and selective dopamine uptake inhibitors. J. Med. Chem. 38 (1995) 3933–3940.

    Article  PubMed  CAS  Google Scholar 

  78. Reith, M. E. A., de Costa, B., Rice, K. C., and Jacobson, A. E. Evidence for mutually exclusive binding of cocaine, BTCP, GBR 12935, and dopamine to the dopamine transporter. Eur. J. Pharmacol.—Mol. Pharmacol. Sec. 227 (1992) 417–425.

    Article  CAS  Google Scholar 

  79. Reith, M. E. A., Meisler, B. E., Sershen, H., and Lajtha, A. Structural requirements for cocaine congeners to interact with dopamine and serotonin uptake sites in mouse brain and to induce stereotyped behavior. Biochem. Pharmacol. 35 (1986) 1123–1129.

    Article  PubMed  CAS  Google Scholar 

  80. Ritz, M. C., Cone, E. J., and Kuhar, M. J. Cocaine inhibition of ligand binding at dopamine, norepinephrine and serotonin transporters: a structure-activity study. Life Sci. 46 (1990) 635–645.

    Article  PubMed  CAS  Google Scholar 

  81. Ritz, M. C., Lamb, R. J., Goldberg, S. R., and Kuhar, M. J. Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237 (1987) 1219–1223.

    Article  PubMed  CAS  Google Scholar 

  82. Rothman, R. B., Becketts, K. M., Radesca, L. R., de Costa, B. R., Rice, K. C., Carroll, F. I., and Dersch, C. M. Studies of the biogenic amine transporters. II. A brief study on the use of [3H]DA-uptake-inhibition to transporter-binding-inhibition ratios for the in vitro evaluation of putative cocaine antagonists. Life Sci 53 (1993) PL267–PL272.

    Google Scholar 

  83. Rothman, R. B., Lewis, B., Dersch, C., Xu, H., Radesca, L., de Costa, B. R., Rice, K. C., Kilburn, R. B., Akunne, H. C., and Pert, A. Identification of a GBR 12935 homolog LR1111 which is over 4,000-fold selective for the dopamine transporter, relative to serotonin and norepinephrine transporters. Synapse 14 (1993) 34–39.

    Article  PubMed  CAS  Google Scholar 

  84. Schweri, M. M., Skolnick, P., Rafferty, M. F., Rice, K. C., Janowsky, A. J., and Paul, S. M. [3H]Threo-(±)-methylphenidate binding to 3,4-dihydroxyphenylethylamine uptake sites in corpus striatum correlation with the stimulant properties of ritalinic acid esters. J. Neurochem. 45 (1985) 1062–1070.

    Article  PubMed  CAS  Google Scholar 

  85. Shimada, S., Kitayama, S., Lin, C.-L., Patel, A., Nanthakumar, E., Gregor, P., Kuhar, M., and Uhl, G. Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA. Science 254 (1991) 576–578.

    Article  PubMed  CAS  Google Scholar 

  86. Simoni, D., Stoelwinder, J., Kozikowski, A. P., Johnson, K. M., Bergmann, J. S., and Ball, R. G. Methoxylation of cocaine reduces binding affinity and produces compounds of differential binding and dopamine uptake inhibitory activity: discovery of a weak cocaine “antagonist”. J. Med. Chem. 36 (1993) 3975–3977.

    Article  PubMed  CAS  Google Scholar 

  87. Stoelwinder, J., Roberti, M., Kozikowski, A. P., Johnson, K. M., and Bergmann, J. S. Differential binding and dopamine uptake activity of cocaine analogues modified at nitrogen. Bioorg. Med. Chem. Lett. 4 (1994) 303–308.

    Article  CAS  Google Scholar 

  88. Usdin, T. B., Mezey, E., Chen, C., Brownstein, M. J., and Hoffman, B. J. Cloning of the cocaine-sensitive bovine dopamine transporter. Proc. Natl. Acad Sci. 88 (1991) 11,168–11,171.

    Google Scholar 

  89. Van der Zee, P., and Hespe, W. Interactions between substituted 1-[2-(diphenylmethoxy)ethyl]piperazines and dopamine receptors. Neuropharmacology 24 (1985) 1171–1174.

    Article  PubMed  Google Scholar 

  90. Van der Zee, P., Koger, H. S., Gootjes, J., and Hespe, W. Aryl 1,4dialk(en)ylpiperazines as selective and very potent inhibitors of dopamine uptake. Eur. J. Med. Chem. 15 (1980) 363–370.

    Google Scholar 

  91. Vandenbergh, D. J., Persico, A. M., Hawkins, A. L., Griffin, C. A., Li, X., Jabs, E. W., and Uhl, G. R. Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. Geonomics 14 (1992) 1104–1106.

    Article  CAS  Google Scholar 

  92. Vignon, J., Cerruti, C., Chaudieu, I., Pinet, V., Chicheportiche, M., Kamenka, J.-M., and Chicheportiche, R. Interaction of molecules in the phencyclidine series with the dopamine uptake system. Correlation with their binding properties to the phencyclidine receptor. Binding properties of 3H-BTCP, a new PCP analog, to the dopamine uptake complex. In Domino, E. F., and Kamenka, J.-M. (eds.), Sigma and Phencyclidine-Like Compounds as Molecular Probes in Biology, NPP Books, Ann Arbor, MI, 1988, pp. 199–208.

    Google Scholar 

  93. Vignon, J. and Lazdunski, M. Structure—function relationships in the inhibition of synaptosomal dopamine uptake by phencyclidine and analogues: Potential correlation with binding sites identified with [3H]phencyclidine. Biochem. Pharmacol. 33 (1984) 700–702.

    Article  PubMed  CAS  Google Scholar 

  94. Vignon, J., Pinet, V., Cerruti, C., Kamenka, J.-M., and Chicheportiche, R. [3H]N[1-(2-Benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP): a new phencyclidine analog selective for the dopamine uptake complex. Eur. J. Pharmacol. 148 (1988) 427–436.

    Article  CAS  Google Scholar 

  95. Xu, C., Coffey, L. L., and Reith, M. E. A. Translocation of dopamine and binding of 2ß-carbomethoxy-313-(4-fluorophenyl)tropane (WIN 35,428) measured under identical conditions in rat striatal synaptosomal preparations. Inhibition by various blockers. Biochem. Pharmacol. 49 (1995) 339–350.

    Article  PubMed  CAS  Google Scholar 

  96. Yu, D. W., Gatley, S. J., Wolf, A. P., MacGregor, R. R., Dewey, S. L., Fowler, J. S., and Schlyer, D. J. Synthesis of carbon-11 labeled iodinated cocaine derivatives and their distribution in baboon brain measured using positron emission tomography. J. Med. Chem. 35 (1992) 2178–2183.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. F. Ivy Carroll
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anita H. Lewin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael J. Kuhar
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. College of Medicine, University of Illinois, Peoria, IL, USA

    Maarten E. A. Reith

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Springer Science+Business Media New York

About this chapter

Cite this chapter

Carroll, F.I., Lewin, A.H., Kuhar, M.J. (1997). Dopamine Transporter Uptake Blockers. In: Reith, M.E.A. (eds) Neurotransmitter Transporters. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-470-2_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-470-2_9

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4757-5980-8

  • Online ISBN: 978-1-59259-470-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation