Return to search

Inhibition of D-Amino acid oxidase by phenothiazines

Thesis (Ph.D.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Although the pharmacology and chemical effects of the phenothiazine derivatives have been extensively studied, very little is known concerning the biochemical mechanisms by which they exert their pharmacological effects. Underlying most of the work in this field is the belief that these compounds have certain enzymes as their primary targets or receptor sites. Thus chlorpromazine (CP Z) has been found to inhibit a wide variety of enzymes including cytochrome oxidase, glucose-phosphate dehydrogenase, hexokinase, and ATPase and to uncouple oxidative phosphorylation. However, excessive concentrations of CPZ were required to inhibit these systems and in most cases there was no good correlation between the antipsychotic behavior of these derivatives and their inhibitory capacity.
Although the differences in inhibitory potency can not be explained yet in terms of binding sites, the approximate correlation between Ki and the usual daily dosage of these compounds in antipsychotic therapy, the failure of phenothiazines with little (if any) tranquilization properties to inhibit D-AAO, and the fact that the concentrations of drug required for inhibition (Ki) were well within the range which may be encountered in vivo all make more tenable the hypothesis that the phenothiazine tranquilizers might exert their effects by inhibiting flavo enzymes. [TRUNCATED] / 2031-01-01

Identiferoai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/36846
Date January 1966
CreatorsHarris, Sheldon R.
PublisherBoston University
Source SetsBoston University
Languageen_US
Detected LanguageEnglish
TypeThesis/Dissertation

Page generated in 0.0024 seconds