The historical development, uses, pharmacology, chemistry and metabolism of phanothiazine and the phenothiazine tranquillisers are reviewed along with the analytical techniques which have been used for their detection and determination. The metabolism and excretion by the horse of promazine chlorpromazine, acepramazine and propionylpromazine, tranquillisers commonly used in equine practice, have been examined qualitatively and quantitatively. Methods of collection, storage and analysis of horse urine have been developed, and the use of mass spectroscopy in combination with gas liquid chromatography for the detection of phenothiazine derivatives in biological fluids has been examined. Qualitative results have shown that many biotransformations of such derivatives take place in the horse. 30 metabolites of promazine were detected in addition to the parent drug, 20 of chlorpromazine and 11 and 6 respectively from acepromazine and propion ylpromazine. Hydroxylation followed by conjugation, prademinantly with glucoronic acid and to a smaller extent with sulphuric acid, is the major route of metabolism of promazine and chlorpromazine. Acapromazine and propionylpromezine, on the other hand, are not conjugated to a great extent. Instead they lose the side chain ketone grouping attached to the nucleus at the 2-position and are excreted in the sulphoxide form. Quantitative results have shown that excretion is irregular and prolonged, in some cases lasting for a week after administration. The percentage of dose detected as urinary metabolites res low, being approximately 19% for chlorpromazine, 10% for promazine and 3% for acepromazine. Conjugated metabolites were excreted predominantly as sulphide derivatives, whereas the unconjugated fraction were predominantly in the sulphoxide form. The applicability of the techniques used for the detection of phenothiazine derivatives, after administration in small doses just sufficient to produce an effect, has also been examined.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:754298 |
| Date | January 1970 |
| Creators | Weir, John J. R. |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/30711/ |
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