Record Details
In vivo and in vitro metabolism of 4-benzo(b)thienyl-N-methylcarbamate and 4-hydroxy benzothiophene by the white rat
ScholarsArchive at Oregon State University
| Field | Value |
|---|---|
| Title | In vivo and in vitro metabolism of 4-benzo(b)thienyl-N-methylcarbamate and 4-hydroxy benzothiophene by the white rat |
| Names |
Miaullis, John Bartley
(creator) Terriere, Leon C. (advisor) |
| Date Issued | 1968-03-27 (iso8601) |
| Note | Graduation date: 1968 |
| Abstract | In vitro studies of Mobam (4-benzo(b)thienyl N-methylcarbamate) metabolism have demonstrated that at least three ether soluble metabolites are formed in a microsomal system fortified with reduced triphosphopyridine nucleotide (NADPH). One of the metabolites was identical to 4HBT (4-hydroxy benzothiophene), the phenol of Mobam. The other two metabolites did not possess the carbonyl carbon of Mobam and therefore involved hydrolysis of the ester linkage. Water soluble metabolites of Mobam and 4HBT were produced by NADPH-dependent microsomal reactions. One of the metabolites contained the carbonyl carbon of Mobam but not the ring moiety. The added cofactors UDPGA (uridine diphosphoglucuronic acid) and ATP/SO₄[subscript =]/Mg⁺⁺ resulted in the formation of specific metabolites of the ring moiety. One of these products is tentatively identified as the glucuronide of 4HBT. No reaction between the carbamic acid portion of the carbamate and UDPGA was observed. In vivo metabolism of Mobam or 4HBT led to the rapid excretion or expiration of the metabolic products. Approximately 80% of the ring moiety and more than 40% of the carbonyl carbon were excreted in the urine within 72 hours after treatment of the rat. An additional one-fourth of the carbonyl carbon was expired as carbon dioxide indicating hydrolysis of the ester linkage and splitting of the C-N bond of the carbamic acid. Besides expired carbon dioxide, four other in vivo metabolites were characterized by their paper chromatographic Rf values. One of these metabolites arose from the carbamic acid moiety and the other three contained the ring structure but not the carbonyl carbon. One of the ring metabolites is tentatively identified as the glucuronide of 4HBT and another may be the sulfate conjugate of 4HBT. Each of the major metabolites of Mobam was also excreted by rats treated with 4HBT, demonstrating the close relationship between the metabolic fate of Mobam and its phenol. |
| Genre | Thesis/Dissertation |
| Topic | Metabolism |
| Identifier | http://hdl.handle.net/1957/47413 |
