Identification of the major metabolites of [3H]-(+)-8-chloro-5-(2,3- dihydrobenzofuran-7-yl)-7-methoxymethyloxy-3-methyl-2,3,4,5-tetrahydro- 1H-3- benzazepine in rats.
1. The in vivo urinary metabolites of 3H(+)-8-chloro-5(2,3- dihydrobenzofuran-7-yl)-7-methoxymethyloxy-3-methyl-2,3,4,5-tetrah ydro-1H-3- benzazepine isolated from Wistar rats have been characterized by mass spectrometry and n.m.r. spectroscopy. 2. Metabolites are formed by N-demethylation, hydroxylation of the dihydrobenzofuran moiety, and elimination of the methoxymethyl group followed by glucuronidation. All combinations of these metabolic pathways were found in the metabolites in urine. 3. In the faeces metabolites formed by hydroxylation of the dihydrobenzofuran moiety and elimination of the methoxymethyl moiety dominate, while N-demethylated metabolites are present only in small amounts. 4. The major plasma metabolite was formed by elimination of the methoxymethyl group followed by glucuronidation. Only minute amounts of other metabolites were present.
Nordholm
L
L
Department of Drug Metabolism, Novo Nordisk CNS Division, Måløv, Denmark.
Wassmann
O
O
Nielsen
P G
PG
Thøgersen
H
H
Grønvald
F
F
D000818:Animals; D001552:Benzazepines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001572:Benzofurans / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D018492:Dopamine Antagonists; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1; D016339:Spectrometry, Mass, Fast Atom Bombardment
D001552:Benzazepines; D001572:Benzofurans; D018492:Dopamine Antagonists; D011355:Prodrugs; D017447:Receptors, Dopamine D1; C076012:7-chloro-5-(2,3-dihydrobenzofuran-7-yl)-7-methoxymethyloxy-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine