Principal component analysis differentiates the receptor binding profiles of three antipsychotic drug candidates from current antipsychotic drugs

J Med Chem. 2007 Oct 18;50(21):5103-8. doi: 10.1021/jm070516u. Epub 2007 Sep 19.

Abstract

The receptor binding affinities of the three drug candidates 1 (SLV310), 2 (SLV313), and 3 (SLV314) were positioned against the results from nine (a)typical antipsychotic drugs. The receptor binding data from sixteen monoaminergic receptors served as the input in a principal component analysis (PCA). The PCA outcome revealed a unique binding profile of 1, 2, and 3 as compared with the reference compounds 4-8 and 10-12. The weight gain inducing antipsychotics 6-8 clustered in the PCA by scoring strongly negative for factor 1. The hyperprolactinaemia related antipsychotics 4, 5, 10, and 12 clustered by their negative scores for factor 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / chemistry*
  • Antipsychotic Agents / metabolism
  • Basal Ganglia Diseases / chemically induced
  • Benzoxazines / adverse effects
  • Benzoxazines / chemistry*
  • Benzoxazines / metabolism
  • Biogenic Monoamines / metabolism
  • Humans
  • Hyperprolactinemia / chemically induced
  • Indoles / adverse effects
  • Indoles / chemistry*
  • Indoles / metabolism
  • Metabolic Diseases / chemically induced
  • Phthalimides / adverse effects
  • Phthalimides / chemistry*
  • Phthalimides / metabolism
  • Piperazines / adverse effects
  • Piperazines / chemistry*
  • Piperazines / metabolism
  • Principal Component Analysis
  • Pyridines / adverse effects
  • Pyridines / chemistry*
  • Pyridines / metabolism
  • Radioligand Assay
  • Receptors, Biogenic Amine / chemistry*
  • Receptors, Biogenic Amine / metabolism
  • Weight Gain

Substances

  • 1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-((5-(4-fluorophenyl)-3-pyridinyl)methyl)piperazine
  • 2-(4-(4-(5-fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-yl)butyl)-phthalimide
  • 8-(4-(3-(5-fluoro-1H-indol-3-yl)propyl)piperazin-1-yl)-4H-benzo(1,4)oxazin-2-methyl-3-one
  • Antipsychotic Agents
  • Benzoxazines
  • Biogenic Monoamines
  • Indoles
  • Phthalimides
  • Piperazines
  • Pyridines
  • Receptors, Biogenic Amine