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[Relationship between perazine serum concentration and clinical results in long-term treated schizophrenic outpatients (author's transl)].

The perazine serum concentration was determined with a new gaschromatographic method in 33 schizophrenic outpatients of our psychiatric catamnestic unit who had received perazine for a period of 18 years. A very high constancy of the perazine serum level could be demonstrated by repeated measurements. A close connection existed between perazine dosage and perazine serum level. Both findings suggest a very good complicance of these patients. Serum levels were correlated positively with the intensity of the psychopathologic symptoms as well as with the frequency of side-effects, particularly with slight changes of liver enzymes.

Adolescent↗

[Effects of neuroleptics on liver function, the hematopoietic system, blood pressure and temperature regulation. Comparison of clozapine, perazine and haloperidol by evaluating medical records].

The frequency of disturbances of the liver function, of leucopoiesis, blood pressure and temperature regulation under clozapine in comparison with perazine and haloperidol in 478 patients (partly being treated repeatedly) was investigated by means of case histories of the Psychiatric Clinic of Tübingen from October 1974 up to June 1978. Within the time of the investigation no case of jaundice arose, however non-symptomatic increases of the liver values could be observed. The three drugs did not differ in this respect. Within the time of the investigation no case of agranulocytosis was observed. Only one leucopenia under clozapine, one under perazine, and six under haloperidol occurred. Concerning cardio-vascular effects of the neuroleptic medication, in 4.1% of the patients under clozapine therapy, 4.3% under haloperidol therapy and 10.3% under perazine therapy hypotension could be observed. Under clozapine 15.2% of the patients showed a rise of temperature, under perazine 3.2% and under haloperidol 2.8% of the patients. 83.3% of cases with elevated temperature under clozapine occurred during the first two weeks of treatment.

Adult↗

Prediction and evaluation criteria in perazine therapy of acute schizophrenics: psychopathological results.

In a pharmacopsychiatric pilot study 28 patients with an acute schizophrenic illness were treated for 4 weeks with perazine (Taxilan). Research goals in the psychopathological investigation were: (1) to assess the range of efficacy, target symptoms and syndromes of perazine and to compare these results with previous studies; (2) to compare the quality, interrater reliability, and practicability of two instruments of psychopathological assessment (AMDP and BPRS) for measuring change during treatment; (3) to apply new mathematical methods for finding statistically significant changes in symptomatology on the item level as well as on the levels of syndrome and total score; (4) to test whether pre-treatment prediction based on psychopathological evaluation or psychophysiological data is possible. The target symptoms and syndromes of perazine were the "positive" schizophrenic syndromes, above all thought disturbances and delusional phenomena. This result was consistent with a former perazine investigation. The BPRS proved to be a practicable and reliable instrument for a more global evaluation of change in psychopathology. The AMDP seemed to be especially useful for evaluating the homogeneity of a sample and showing differentiated psychopathological profiles. On this scale, changes in symptomatology became statistically apparent more clearly and more quickly on the syndrome level rather than on the level of single items. As to interrater reliability, both scales perform well. Dichotomizing the original scaling may mean a loss of information from both scales (AMDP and BPRS) in their evaluation of change. Hence it seems necessary to introduce new mathematical procedures (e.g., Friedman and Dunn-Rankin tests) into pharmacopsychiatric research.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Specific binding of perazine, a piperazine side-chain phenothiazine drug, to a serum protein (author's transl)].

A binding of perazine to a serum protein of 48 000 D was determined by gel filtration. The affinity constant of the perazine-protein complex was found to be 5.42 X 10(6) mol/l corresponding to a specific binding of 70 ng/ml serum. This result may gather clinical relevance with regard to the "CNS-bioavailability" and individual response to perazine, the average therapeutic serum concentrations having been shown to range between appr. 50 and 200 ng/ml serum. A specific binding of perazine to human or bovine albumine could not be detected.

Antipsychotic Agents↗

[Fatal poisoning with clozapine and perazine. A case report].

An intoxication following an apparent overdose of clozapine (Leponex) and perazine (Taxilan) is reported. There was a wide range of variation in postmortem blood and tissue concentrations of clozapine, desmethyclozapine and perazine. Clozapine/norclozapine blood and tissue ratios and perazine-pill-fragments in the gastric content could be used as a sign of suspected acute clozapine and perazine overdose.

Adult↗

Single-dose kinetics of the neuroleptic drug perazine in psychotic patients.

Eight male and two female unmedicated psychotic patients received 100 mg perazine orally and seven blood samples were taken within 25 h. Plasma levels of perazine and its demethylated metabolite were analyzed by HPLC with electrochemical detection. They exhibited large interindividual variations, with maximal concentrations as well as AUC values of perazine differing more than 10-fold. From the decay of plasma levels during the last 12-18 h half-lives were estimated to be between 7.5 and 10 h; they did not correlate with AUC. There was a significant positive correlation between AUC and age. Desmethylperazine was consistently present at lower concentrations than the parent drug during the first 12 h.

Adult↗

Binding of perazine to alpha 1-acid glycoprotein.

The high-affinity binding of perazine to human serum-protein (non-albumin binding) was previously investigated by gel-chromatography. The immunoelectrophoretic identification of the binding agent as alpha 1-acid glycoprotein is described here. It was demonstrated by equilibrium dialysis that the average free fraction of 3H-perazine added to 22 sera from patients before neuroleptic treatment was 3.67 +/- 0.42%, and that there was a significant correlation between the alpha 1-acid glycoprotein content and the free fraction in these serum samples. This result is in accordance with what others have found for imipramine. It is suggested that the nature of this binding should be studied in more detail, since specific binding to alpha 1-acid glycoprotein may be related to the receptor binding of perazine and possibly other drugs.

Antipsychotic Agents↗

Pharmacological studies on perazine and its primary metabolites.

The study served to answer the question whether metabolites possibly contribute to the clinical actions of the neuroleptic drug perazine. The primary metabolites demethylperazine and perazine sulfoxide were investigated with regard to influences on behavior in mice, to an antiemetic action in dogs, and to a modification of the pressor effect of noradrenaline in rats. In contrast to perazine, none of the metabolites exhibited effects that can be interpreted to indicate neuroleptic or antidepressive properties of the compounds.

Animals↗

A unique case of tardive dystonia induced by short-term therapy with perazin.

Perazin is a piperazine derivative of phenothiazine with higher affinity for the D2 than the D1 receptor. We observed a 43-year-old woman who developed blepharospasm and oral hyperkinesia as a tardive dystonic syndrome after short-term treatment with perazin. She had never taken any other neuroleptic medication and all known forms of secondary dystonia were ruled out. We were unable to find any previous reports of perazin-induced tardive dystonia.

Adult↗

Thin-layer and gas-liquid chromatographic procedures for the determination of perazine and its metabolites in human body fluids.

The quantitative determination of perazine, a neuroleptic drug, and its metabolites in body fluids is difficult in view of the low concentrations to be expected under therapeutic conditions as well as of the problem of convenient detectors. Different methods for extraction and measurement of perazine concentration in blood samples are discussed, with special consideration of partition coefficients and the properties of the chromatographic systems (thin-layer and gas-liquid chromatography). A new and simple method for rapid gas chromatographic determination of perazine is presented.

Antipsychotic Agents↗

Photo-decomposition and metabolism of the phenothiazine drug perazine.

An ethanolic solution of perazine (Taxilan), degraded by photooxidation, was examined by HPLC and mass-spectroscopy. Identical degradation and oxidation products were found in vitro as reported to exist in vivo with the exception of perazine-N-oxide and 3-OH-perazine. The formation of the latter two metabolites seems to be bound to the cytochrome P-450 system. A direct, oxygen dependent formation of some metabolites is, however, suggested. Side-effects of phenothiazines such as contact allergies might be related to the formation of radicals or particular oxidation products.

Animals↗

Outcome and risks of ultra-long-term treatment with an oral neuroleptic drug. Relationship between perazine serum levels and clinical variables in schizophrenic outpatients.

In 33 schizophrenic patients treated continuously as outpatients with perazine over two decades, the rehospitalization rate decreased from 0.58 before treatment to 0.07 during treatment. The intensity of psychopathologic symptoms and the side effects were found to be remarkably low. The high intraindividual constancy of perazine plasma levels and the tight correlation between dose and plasma levels indicated satisfactory patient compliance. Plasma levels amounted to only 25% of those under acute treatment and correlated positively with the severity of the disease. Higher plasma levels coincided with more frequent side effects such as slightly pathologic liver function and moderate impairment of oral glucose tolerance. The results suggest that low-dose maintenance treatment of schizophrenic patients with oral neuroleptics is effective and relatively safe.

Adult↗

[Effectiveness and tolerance of zotepine in a double-blind comparison with perazine in schizophrenic patients].

40 inpatients suffering from a schizophrenia (ICD-9) were treated with either zotepine or perazin. The study was continued for a period of 28 days. Assessment of clinical efficacy was effected via BPRS, AMDP, CGI and SANS; tolerance was assessed by means of Simpson's scale. In addition, EEG, ECG and laboratory controls were conducted. The overall therapeutic efficacy was good, and it was not possible to distinguish one group from the other, i.e. both substances were equally effective, judged by means of the psychopathometric tools that were at our disposal. In 11 patients of the zotepine group and in 9 patients of the perazin group, slight extrapyramidal symptoms were observed. No clinically relevant changes were seen in EEG, ECG and laboratory controls in both groups.

Adult↗

Prediction and evaluation criteria in perazine therapy of acute schizophrenics. Methodological considerations, sample population, and research variables.

In an open study of schizophrenic patients treated with perazine (Taxilan), a multidimensional approach comprising the following three areas was chosen: 1. psychopathology (AMDP, BPRS); 2. psychophysiology (habituation of skin resistance reaction, pulse rate); 3. pharmacokinetics (perazine-desmethylperazine plasma levels). Looking beyond the known global effect of the neuroleptic drug, interactions between these three areas were studied. Furthermore, methodological questions concerning possible predictor variables for treatment outcome were examined. Finally, an improved method for analyzing psychopathological data was employed. The methodological framework of the study, the examination techniques, and patient population are presented.

Acute Disease↗

Determination of perazine serum levels by gas liquid chromatography under clinical routine conditions.

A quantitative gas liquid chromatographic method for the determination of serum levels of perazine (10-[3'-(1''-methyl-4''-piperazinyl)-propyl]-phenothiazine) is described. Perazine is used as a neuroleptic drug. The main problem consists in optimizing the chromatographic system. A sensitivity of appr. 60--150 nmol/1 (20--50 microgram/1) serum is achieved. Examples of optimization, analyses with patient samples, and the reproducibility of the results are presented.

Antipsychotic Agents↗

Examination of iron (III) and hexacyanoferrate (III) ions as reagents for the spectrophotometric determination of promazine and perazine.

Iron (III) chloride and potassium hexacyanoferrate (III) have been tested as reagents for the determination of promazine hydrochloride and perazine. The methods are based on the oxidation of phenothiazines by FeCl3 and K3[Fe(CN)6] in perchloric acid medium. The optimal conditions for the formation of oxidation products of promazine and perazine were examined. The absorption spectra in the UV-VIS region were recorded.

Chlorides↗

Kinetics of drug decomposition. Part 46. Photooxidation and photolysis of some perazine derivatives.

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.

Antipsychotic Agents↗

[Perazine-induced agranulocytosis--case report and discussion].

A 22-year-old female patient developed agranulocytosis 26 days after starting single agent treatment with perazine. In accordance with the clinical and hematological picture this agranulocytosis is classified as antibody mediated with destruction of peripheral neutrophils. After cessation of perazine treatment and proper therapy of infection the patient recovered within two weeks. The diagnosis of agranulocytosis should be suspected in anyone on neuroleptic treatment who develops fever, malaise or objective evidence of an infection and in neutropenic patients the adequate treatment should be started immediately.

Adult↗