Chlorpromazine and dopamine: conformational similarities that correlate with the antischizophrenic activity of phenothiazine drugs.
Phenothiazines and butyrophenones are known to alter dopamine (3,4-dihydroxyphenethylamine) metabolism in the brain in a fashion suggesting that they may block dopamine receptors. We observed, using Dreiding molecular models, that dopamine in its solid-state conformation is superimposable upon a portion of the known x-ray structure of chlorpromazine [2-chloro-10-(3-dimethylaminopropyl)-phenothiazine]. The ability of phenothiazine drugs to mimic the dopamine-like conformation correlates with their antischizophrenic efficacy. These structure-activity relationships explain the importance of a substituent in ring a, a three-carbon side chain bearing the amino group, and a hetero atom between rings a and c.
D001665:Binding Sites; D002746:Chlorpromazine / Q000032:analysis* / Q000494:pharmacology; D003990:Dibenzoxepins / Q000032:analysis; D004298:Dopamine / Q000032:analysis* / Q000494:pharmacology; D006220:Haloperidol / Q000032:analysis; D006801:Humans; D007536:Isomerism; D008961:Models, Structural; D012559:Schizophrenia / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction; D014966:Xanthenes / Q000032:analysis
D003990:Dibenzoxepins; D014966:Xanthenes; D006220:Haloperidol; D002746:Chlorpromazine; D004298:Dopamine