Partitioning behaviour of local anesthetic fomocaine derivatives.
The octanol/water partitioning behaviour of local anesthetic fomocaine derivatives has been investigated. The true partition coefficients obtained from log P(app) values reflect well the high lipophilicity of these aminoalkylaryl-ether type compounds. A consequence of this is that the partitioning of the protonated form is not negligible as was proved by the log P(i) values of the ionized molecule measured at pH 4.0. The effect of ionization on partitioning was studied and characterized by the pQ values. This ionization influence on lipophilicity was found quite constant (pQ approximately 4) among the hydroxypiperidine analogs. A parabolic relationship was obtained between the acute toxicity and the log P values of several of the examined compounds.
Takács-Novák
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Institute of Pharmaceutical Chemistry, Semmelweis University of Medicine, Budapest, Hungary.
Oelschläger
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Budvári-Bárány
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Szász
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D000779:Anesthetics, Local / Q000737:chemistry* / Q000633:toxicity; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003315:Cornea / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D010647:Phenyl Ethers / Q000737:chemistry* / Q000633:toxicity; D011817:Rabbits; D013329:Structure-Activity Relationship
D000779:Anesthetics, Local; D010647:Phenyl Ethers; C100275:fomocain