Structure-Toxicity Relationships of Substituted Phenothiazines

• Published in: Journal of pharmaceutical sciences 1972-09, Vol.61 (9), p.1498-1499
• Main Authors: Nightingale, Charles H., Tse, Melissa, Stupak, Elliot I.
• Format: Article
• Language: English
• Subjects: Animals; Cyprinidae; dodecane-correlated with goldfish test system data; goldfish test system data correlated with dodecane partition coefficients; Hydrogen-Ion Concentration; Partition coefficients; Partition coefficients, dodecane—correlated with goldfish test system data, structure-toxicity relationships of substituted phenothiazine derivatives; Phenothiazine derivatives; Phenothiazine derivatives, substituted—structure-toxicity relationships, goldfish test system data correlated with dodecane partition coefficients; Phenothiazines - toxicity; Structure-Activity Relationship; structure-toxicity relationships of substituted phenothiazine derivatives; Structure-toxicity relationships-substituted phenothiazine derivatives; Structure-toxicity relationships—substituted phenothiazine derivatives, goldfish test system data correlated with dodecane partition coefficients; substituted-structure-toxicity relationships; Surface Properties; Surface Tension; Time Factors
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600610939

The goldfish test system is capable of discerning structure-toxicity relationships of substituted phenothiazine derivatives. A rank order correlation between dodecane partition coefficients, surface activity, and toxicity in goldfish was observed for various 2-substituted chlorpromazine derivatives (triflupromazine > chlorpromazine > promazine > chlorpromazine sulfoxide). Dodecane partition coefficients were also found to correlate with the death of goldfish induced by the 1-chloro, 2-chloro, and 3-chloro analogs of chlorpromazine. The data imply that differences in the absorption of the phenothiazines could account, in part, for the observed differences in toxicity.