Principal component analysis differentiates the receptor binding profiles of three antipsychotic drug candidates from current antipsychotic drugs.
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.
Lange
Jos H M
JH
Solvay Pharmaceuticals, Research Laboratories, C. J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands. jos.lange@solvay.com
Reinders
Jan-Hendrik
JH
Tolboom
Jeroen T B M
JT
Glennon
Jeffrey C
JC
Coolen
Hein K A C
HK
Kruse
Chris G
CG
D014150:Antipsychotic Agents / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D048588:Benzoxazines / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D015306:Biogenic Monoamines / Q000378:metabolism; D006801:Humans; D006966:Hyperprolactinemia / Q000139:chemically induced; D007211:Indoles / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D008659:Metabolic Diseases / Q000139:chemically induced; D010797:Phthalimides / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D010879:Piperazines / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D025341:Principal Component Analysis; D011725:Pyridines / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism; D011869:Radioligand Assay; D017982:Receptors, Biogenic Amine / Q000737:chemistry* / Q000378:metabolism; D015430:Weight Gain
C504317:1-(2,3-dihydro-1,4-benzodioxin-5-yl)-4-((5-(4-fluorophenyl)-3-pyridinyl)methyl)piperazine; C476321:2-(4-(4-(5-fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-yl)butyl)-phthalimide; C506289:8-(4-(3-(5-fluoro-1H-indol-3-yl)propyl)piperazin-1-yl)-4H-benzo(1,4)oxazin-2-methyl-3-one; D014150:Antipsychotic Agents; D048588:Benzoxazines; D015306:Biogenic Monoamines; D007211:Indoles; D010797:Phthalimides; D010879:Piperazines; D011725:Pyridines; D017982:Receptors, Biogenic Amine