Sigma-1 and dopamine D2/D3 receptor occupancy of pridopidine in healthy volunteers and patients with Huntington disease: a [18F] fluspidine and [18F] fallypride PET study

  1. Grachev, Igor D.
  2. Meyer, Philipp M.
  3. Becker, Georg A.
  4. Bronzel, Marcus
  5. Marsteller, Doug
  6. Pastino, Gina
  7. Voges, Ole
  8. Rabinovich, Laura
  9. Knebel, Helena
  10. Zientek, Franziska
  11. Rullmann, Michael
  12. Sattler, Bernhard
  13. Patt, Marianne
  14. Gerhards, Thilo
  15. Strauss, Maria
  16. Kluge, Andreas
  17. Brust, Peter
  18. Savola, Juha-Matti
  19. Gordon, Mark F.
  20. Geva, Michal
  21. Hesse, Swen
  22. Barthel, Henryk
  23. Hayden, Michael R.
  24. Sabri, Osama

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1000 Titel
  • Sigma-1 and dopamine D2/D3 receptor occupancy of pridopidine in healthy volunteers and patients with Huntington disease: a [18F] fluspidine and [18F] fallypride PET study
1000 Autor/in
  1. Grachev, Igor D. |
  2. Meyer, Philipp M. |
  3. Becker, Georg A. |
  4. Bronzel, Marcus |
  5. Marsteller, Doug |
  6. Pastino, Gina |
  7. Voges, Ole |
  8. Rabinovich, Laura |
  9. Knebel, Helena |
  10. Zientek, Franziska |
  11. Rullmann, Michael |
  12. Sattler, Bernhard |
  13. Patt, Marianne |
  14. Gerhards, Thilo |
  15. Strauss, Maria |
  16. Kluge, Andreas |
  17. Brust, Peter |
  18. Savola, Juha-Matti |
  19. Gordon, Mark F. |
  20. Geva, Michal |
  21. Hesse, Swen |
  22. Barthel, Henryk |
  23. Hayden, Michael R. |
  24. Sabri, Osama |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-09-29
1000 Erschienen in
1000 Quellenangabe
  • 48(4):1103-1115
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00259-020-05030-3 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041674/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Purpose!#!Pridopidine is an investigational drug for Huntington disease (HD). Pridopidine was originally thought to act as a dopamine stabilizer. However, pridopidine shows highest affinity to the sigma-1 receptor (S1R) and enhances neuroprotection via the S1R in preclinical studies. Using [!##!Methods!#!Using [!##!Results!#!S1R occupancy as function of pridopidine dose (or plasma concentration) in HVs could be described by a three-parameter Hill equation with a Hill coefficient larger than one. A high degree of S1R occupancy (87% to 91%) was found throughout the brain at pridopidine doses ranging from 22.5 to 90 mg. S1R occupancy was 43% at 1 mg pridopidine. In contrast, at 90 mg pridopidine, the D2/D3R occupancy was only minimal (~ 3%).!##!Conclusions!#!Our PET findings indicate that at clinically relevant single dose of 90 mg, pridopidine acts as a selective S1R ligand showing near to complete S1R occupancy with negligible occupancy of the D2/D3R. The dose S1R occupancy relationship suggests cooperative binding of pridopidine to the S1R. Our findings provide significant clarification about pridopidine's mechanism of action and support further use of the 45-mg twice-daily dose to achieve full and selective targeting of the S1R in future clinical trials of neurodegenerative disorders. Clinical Trials.gov Identifier: NCT03019289 January 12, 2017; EUDRA-CT-Nr. 2016-001757-41.
1000 Sacherschließung
lokal Neurology
lokal Dopamine D2/D3 receptor occupancy
lokal Huntington disease
lokal Brain/diagnostic imaging [MeSH]
lokal Receptors, Dopamine D3/metabolism [MeSH]
lokal Sigma-1 receptor occupancy
lokal Pridopidine
lokal Humans [MeSH]
lokal Receptors, Dopamine D2/metabolism [MeSH]
lokal Piperidines [MeSH]
lokal Dopamine [MeSH]
lokal PET
lokal Original Article
lokal Male [MeSH]
lokal Brain/metabolism [MeSH]
lokal Benzamides [MeSH]
lokal Healthy Volunteers [MeSH]
lokal Benzofurans [MeSH]
lokal Positron-Emission Tomography [MeSH]
lokal [
lokal Huntington Disease/diagnostic imaging [MeSH]
1000 Liste der Beteiligten
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1000 Erstellt am 2023-11-18T05:06:26.371+0100
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1000 Zuletzt bearbeitet 2023-12-01T11:27:34.442+0100
1000 Objekt bearb. Fri Dec 01 11:27:34 CET 2023
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