Estimation of methotrimeprazine in brain and correlation of brain levels with pharmacologic activity

A method for estimating methotrimeprazine in brain by ultraviolet spectrophotometry was developed which is based on extracting the compound from alkalinized tissue with 1 per cent butanol in cyclohexane and determining its absorbance in acid at 250mμ. A high degree of specificity for methotrimeprazi...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 1967-06, Vol.56 (6), p.720-724
Main Authors: Afifi, Abdel-Halim M., Way, E.Leong
Format: Article
Language:English
Subjects:
Animals
Brain Chemistry
Countercurrent Distribution
Methotrimeprazine - analysis
Methotrimeprazine - pharmacology
Mice
Movement - drug effects
Spectrophotometry
Tissue Extracts - analysis
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Summary:A method for estimating methotrimeprazine in brain by ultraviolet spectrophotometry was developed which is based on extracting the compound from alkalinized tissue with 1 per cent butanol in cyclohexane and determining its absorbance in acid at 250mμ. A high degree of specificity for methotrimeprazine was conveyed to the procedure by subjecting the organic solvent extract of tissue to several buffer washes. Following intravenous injection of the compound in mice, methotrimeprazine was found to be metabolized rapidly during the first hour, after which its rate of disappearance slowed considerably. Brain levels were maximal at 1hr. and were still appreciable at 4hr. The onset and duration of pharmacologic effects as measured by a loss in coordinated motor ability varied directly with the concentration of drug in the brain, suggesting that the parent compound is principally responsible for mediating the response.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.2600560612