Human moricizine metabolism. I. Isolation and identification of metabolites in human urine.
1. Using synthetic standards and/or spectral data, seven moricizine metabolites were structurally identified in human urine. Two novel metabolites were identified as phenothiazine-2-carbamic acid and ethyl [10-(3-aminopropionyl) phenothiazin-2-yl] carbamate. Two novel human moricizine metabolites, 2-amino-10-(3-morpholino-propionyl) phenothiazine, a previously identified dog metabolite, and 2-aminophenothiazine, a previously identified rat metabolite, were also identified. Three additional human metabolites, phenothiazine-2-carbamic acid ethyl ester sulphoxide (P2CAEES), moricizine sulphoxide, and ethyl ¿10-[N-(2'-hydroxyethyl)3-aminopropionyl] phenothiazin-2-yl¿ carbamate, all previously described in the literature, were observed. 2. Both 2-amino-10-(3-morpholinopropionyl) phenothiazine and ethyl [10-(3-aminopropionyl) phenothiazin-2-yl] carbamate, and possibly ethyl ¿10-[N-(2'-hydroxyethyl) 3-aminopropionyl]phenothiazin-2-yl¿ carbamate, possess the structural characteristics thought to be necessary for class 1 antiarrhythmic activity.
Richards
L E
LE
DuPont Merck Pharmaceutical Co., Stine-Haskell Research Center, Newark, USA.
Pieniaszek
H J
HJ
Shatzmiller
S
S
Page
G O
GO
Blom
K F
KF
Read
J M
JM
Davidson
A F
AF
Confalone
P N
PN
D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D015394:Molecular Structure; D016293:Moricizine / Q000008:administration & dosage / Q000378:metabolism*; D011355:Prodrugs / Q000008:administration & dosage / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D011355:Prodrugs; D016293:Moricizine