Artigo Revisado por pares

Ionization constants, octanol partition coefficients and Cholinesterase inhibitor constants for chlorpromazine and its metabolites

1989; Oxford University Press; Volume: 41; Issue: 12 Linguagem: Inglês

10.1111/j.2042-7158.1989.tb06387.x

ISSN

2042-7158

Autores

Robin Whelpton,

Tópico(s)

Molecular Sensors and Ion Detection

Resumo

The relationship between the lipophilic character of chlorpromazine and seven of its metabolites and their ability to inhibit horse serum cholinesterase (Ki) has been investigated. Log(1/Ki) values were correlated with log P octanol partition coefficients (r = 0.88, P less than 0.01, n = 8). The inhibitor values ranged from 2.7 x 10(-6) M for chlorpromazine to 48.6 x 10(-6) M for monodesmethylchlorpromazine sulphoxide. Ionization constants were determined by limiting solubility, spectrophotometry and pH-partition characteristics. Demethylated metabolites were more basic than the tertiary amines and the sulphoxides were slightly less basic than the corresponding sulphides.

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