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Phenylcyclopropylmethylamine

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Lumocaserin, a serotonin 5-HT2C receptor agonist and PCPMA derivative.

Phenylcyclopropylmethylamines (PCPMAs), or 2-phenylcyclopropylmethylamines, are a class of chemical compounds and drugs related to other groups such as phenethylamines and phenylcyclopropylamines (e.g., tranylcypromine, DMCPA).[1]

Drugs of the PCPMA family include serotonin–norepinephrine reuptake inhibitors (SNRIs) (e.g., milnacipran),[1] monoamine oxidase inhibitors (MAOIs),[2] melatonin receptor agonists,[1] neurokinin NK3 receptor antagonists,[1] dopamine D2 receptor agonists,[3] dopamine D3 receptor modulators,[4][5] serotonin 5-HT2C receptor agonists (e.g., lumocaserin),[6][7][8][9][10][11] and sigma σ1 receptor ligands,[1] among others.[1]

PCPMA itself is known to act as a potent and selective serotonin 5-HT2C receptor agonist (and to a lesser extent as a serotonin 5-HT2B receptor agonist), whereas tranylcypromine was more than 500-fold less potent as a serotonin 5-HT2C receptor agonist in comparison.[11]

Chemical synthesis of 2-phenylcyclopropylmethylamines has been reviewed.[12]

References

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  1. 1 2 3 4 5 6 Li H, Cheng J (March 2024). "2-Phenylcyclopropylmethylamine (PCPMA) as a privileged scaffold for central nervous system drug design". Bioorg Med Chem Lett. 101 129654. doi:10.1016/j.bmcl.2024.129654. PMID 38360418.
  2. ↑ Rosen TC, Yoshida S, Kirk KL, Haufe G (August 2004). "Fluorinated phenylcyclopropylamines as inhibitors of monoamine oxidases". ChemBioChem. 5 (8): 1033–1043. doi:10.1002/cbic.200400053. PMID 15300824.
  3. ↑ Yan W, Fan L, Yu J, Liu R, Wang H, Tan L, Wang S, Cheng J (December 2021). "2-Phenylcyclopropylmethylamine Derivatives as Dopamine D2 Receptor Partial Agonists: Design, Synthesis, and Biological Evaluation". J Med Chem. 64 (23): 17239–17258. doi:10.1021/acs.jmedchem.1c01327. PMID 34797051.
  4. ↑ Tan L, Zhou Q, Yan W, Sun J, Kozikowski AP, Zhao S, Huang XP, Cheng J (May 2020). "Design and Synthesis of Bitopic 2-Phenylcyclopropylmethylamine (PCPMA) Derivatives as Selective Dopamine D3 Receptor Ligands". J Med Chem. 63 (9): 4579–4602. doi:10.1021/acs.jmedchem.9b01835. PMID 32282200.
  5. ↑ Guo L, Gao Y, Zhang S, Zhao L, Zhao R, Sun P, Pan X, Zhang W (April 2025). "2-Phenylcyclopropylmethylamine (PCPMA) Derivatives as D3R-Selective Ligands for 3D-QSAR, Docking and Molecular Dynamics Simulation Studies". Int J Mol Sci. 26 (8): 3559. doi:10.3390/ijms26083559. PMC 12026889. PMID 40332026.
  6. ↑ Zhang G, McCorvy JD, Shen S, Cheng J, Roth BL, Kozikowski AP (November 2019). "Design of fluorinated cyclopropane derivatives of 2-phenylcyclopropylmethylamine leading to identification of a selective serotonin 2C (5-HT2C) receptor agonist without 5-HT2B agonism". Eur J Med Chem. 182 111626. doi:10.1016/j.ejmech.2019.111626. PMC 6815260. PMID 31445232.
  7. ↑ Cheng J, Giguere PM, Schmerberg CM, Pogorelov VM, Rodriguiz RM, Huang XP, Zhu H, McCorvy JD, Wetsel WC, Roth BL, Kozikowski AP (January 2016). "Further Advances in Optimizing (2-Phenylcyclopropyl)methylamines as Novel Serotonin 2C Agonists: Effects on Hyperlocomotion, Prepulse Inhibition, and Cognition Models". J Med Chem. 59 (2): 578–591. doi:10.1021/acs.jmedchem.5b01153. PMC 8317212. PMID 26704965.
  8. ↑ Cheng J, Kozikowski AP (December 2015). "We Need 2C but Not 2B: Developing Serotonin 2C (5-HT2C) Receptor Agonists for the Treatment of CNS Disorders". ChemMedChem. 10 (12): 1963–1967. doi:10.1002/cmdc.201500437. PMC 4832415. PMID 26507582.
  9. ↑ Cheng J, Giguère PM, Onajole OK, Lv W, Gaisin A, Gunosewoyo H, Schmerberg CM, Pogorelov VM, Rodriguiz RM, Vistoli G, Wetsel WC, Roth BL, Kozikowski AP (February 2015). "Optimization of 2-phenylcyclopropylmethylamines as selective serotonin 2C receptor agonists and their evaluation as potential antipsychotic agents". J Med Chem. 58 (4): 1992–2002. doi:10.1021/jm5019274. PMC 4834193. PMID 25633969.
  10. ↑ Cheng J, Giguere PM, Lv W, Roth BL, Kozikowski AP (June 2015). "Design and Synthesis of (2-(5-Chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)cyclopropyl)methanamine as a Selective Serotonin 2C Agonist". Tetrahedron Lett. 56 (23): 3420–3422. doi:10.1016/j.tetlet.2015.01.060. PMC 4479288. PMID 26120215.
  11. 1 2 Cho SJ, Jensen NH, Kurome T, Kadari S, Manzano ML, Malberg JE, Caldarone B, Roth BL, Kozikowski AP (April 2009). "Selective 5-hydroxytryptamine 2C receptor agonists derived from the lead compound tranylcypromine: identification of drugs with antidepressant-like action". J Med Chem. 52 (7): 1885–1902. doi:10.1021/jm801354e. PMC 2832311. PMID 19284718.
  12. ↑ Bertus P, Caillé J (March 2025). "Advances in the Synthesis of Cyclopropylamines". Chem Rev. 125 (6): 3242–3377. doi:10.1021/acs.chemrev.4c00674. PMID 40048498.
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