ABSTRACT
Human lymphocyte cultures from 55 schizophrenic subjects and one manic-depressive subject being treated with the phenothiazine derivative perazine and with other drugs were analyzed with respect to chromosomal damage. The frequency of exchange-type aberrations in these subjects was more than double that in clinically normal control subjects. No correlation was detectable between the aberration frequency and sex, age, smoking and drinking habits, and treatment conditions. It is possible that the elevation of the chromosomal aberration frequency is due to perazine. In vitro studies with perazine and two main metabolites (desmethylperazine and perazine sulfoxide) with human lymphocytes and CHO cells with and without metabolic activation by liver microsomes gave negative results with respect to the induction of sister chromatid exchanges. Possible differences in the metabolism of perazine in vivo and in vitro are discussed.
Subject(s)
Antipsychotic Agents/toxicity , Chromosome Aberrations , Mutagens , Perazine/toxicity , Adolescent , Adult , Aged , Animals , Cell Line , Cells, Cultured , Cricetinae , Female , Half-Life , Humans , In Vitro Techniques , Lymphocytes/drug effects , Male , Microsomes, Liver/metabolism , Middle Aged , Ovary , Perazine/analogs & derivatives , Perazine/metabolism , Phenothiazines/metabolism , Phenothiazines/toxicity , Schizophrenia/blood , Sister Chromatid Exchange/drug effectsABSTRACT
Mass spectra of perazine, prochlorperazine, tiethylperazine, trifluperazine, butaperazine and thioproperazine were obtained. All possible fragmentation routes were discussed. The mechanism of fragmentations, their similarities and differences within the investigated group of compounds were established. The Hammett type relationship was found between the intensities of some ions and the kind of substituents at the C2 position. The utility of mass spectra for the prediction of drug stability was demonstrated.
Subject(s)
Antipsychotic Agents/analysis , Perazine/analysis , Chemical Phenomena , Chemistry , Drug Stability , Gas Chromatography-Mass Spectrometry , Mass Spectrometry , Perazine/analogs & derivativesABSTRACT
The rate and type of the photochemical degradation of perazine derivatives in acidic aqueous solutions depends upon the nature of the substituent at C2 atom. Free perazine degrades by two parallel reactions, namely a fast reversible first-order photooxidation and a slow zero-order photolysis. An introduction of the substituent in the C2 position results frequently in the elimination of one of these reactions.
Subject(s)
Antipsychotic Agents/radiation effects , Perazine/radiation effects , Ultraviolet Rays , Drug Stability , Kinetics , Oxidation-Reduction , Perazine/analogs & derivatives , Photochemistry , Photolysis , Time FactorsABSTRACT
A quantum yield phi of photooxidation of perazine derivatives estimated actinometrically and the pKa, values were used for the correlation with the substituent volumes. The Hammett type plots of phi= f(sigma) and phi= f(pKa10--pKa1) are discussed.
Subject(s)
Antipsychotic Agents/radiation effects , Perazine/radiation effects , Ultraviolet Rays , Chemical Phenomena , Chemistry , Drug Stability , Hydrogen-Ion Concentration , Oxidation-Reduction , Perazine/analogs & derivatives , PhotochemistryABSTRACT
A method has been developed for the determination of perazine, clozapine, imipramine and amitriptyline and their demethylated metabolites in plasma. Other metabolites measured were perazine sulfoxide and the N-oxides of clozapine and perazine, the latter two following their reduction to the parent drugs with ascorbic acid. 10-Hydroxynortriptyline was identified as an amitriptyline metabolite in plasma. The general procedure included extraction of alkalinized plasma samples (3 - 6 g) with benzene or toluene and thin layer chromatography of the extracts, followed by reflectance photometry of the plates at appropriate wave lengths in ultraviolet light. Spots of questionable identity were further characterized by two-dimensional chromatography and by colour reactions. Therecoveries of compounds added in therapeutic concentrations were between 70 and 98 %. The limits of detectability were 5 - 10 ng/g plasma.
Subject(s)
Psychotropic Drugs/blood , Amitriptyline/blood , Chromatography, Thin Layer/methods , Clozapine/analogs & derivatives , Clozapine/blood , Desipramine/blood , Humans , Imipramine/analogs & derivatives , Methods , Nortriptyline/blood , Perazine/analogs & derivatives , Perazine/blood , Spectrophotometry, UltravioletABSTRACT
Desmethylperazine (norperazine) and desmethylprochlorperazine (norprochlorperazine), like nor1- and nor2chlorpromazine, are excellent substrates for indolethylamine N-methyltransferase (NMT) and also inhibit the formation of dimethyltryptamine (DMT) from N-methyl-tryptamine (NMT). Nortriptyline and protriptyline, antidepressant compounds which like NMT contain a secondary amino group, also serve as substrates for INMT but lack in inhibitory effect on DMT formation.
