PT  - JOURNAL ARTICLE
AU  - S G Dahl
AU  - M Hjorth
AU  - E Hough
TI  - Chlorpromazine, methotrimeprazine, and metabolites. Structural changes accompanying the loss of neuroleptic potency by ring sulfoxidation.
DP  - 1982 Mar 01
TA  - Molecular Pharmacology
PG  - 409--414
VI  - 21
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/21/2/409.short
4100  - http://molpharm.aspetjournals.org/content/21/2/409.full
SO  - Mol Pharmacol1982 Mar 01; 21
AB  - The 3-dimensional molecular structures of methotrimeprazine, methotrimeprazine sulfoxide, and chlorpromazine sulfoxide were examined by X-ray crystallography. Previous studies of their dopamine receptor binding affinities have indicated that both chlorpromazine sulfoxide and methotrimeprazine sulfoxide lack neuroleptic potency. The crystal structures of methotrimeprazine and its sulfoxide were similar to the previously published structure of chlorpromazine. The sulfoxide metabolite of chlorpromazine, on the other hand, had a different conformation of the side chain. A boat axial conformation of the sulfoxy group was found for both metabolites. The crystal structures suggest that the apparent loss of neuroleptic potency by biotransformation of the phenothiazine drugs to their ring sulfoxides is caused by the introduction of the sulfoxide group itself, and not by concurrent conformational changes in the rest of the molecule.