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PubMedDate not supplied

Liquid chromatographic method for perphenazine and its sulfoxide in pharmaceutical dosage forms for determination of stability.

A liquid chromatographic method is described for determination of perphenazine and perphenazine sulfoxide in representative dosage forms. Sulfoxide levels were nondetectable or less than 1% in tablets and in an injectable product. Sulfoxide levels increase with time in some syrup formulations and may be as high as 11% in syrup formulations before their expiration date.

Chromatography, Liquid↗
PubMed1978

Effects of intravenous cocaine, diethylpropion, d-amphetamine and perphenazine on responding maintained by food delivery and shock avoidance in rhesus monkeys.

The effects of perphenazine, cocaine, diethylpropion and d-amphetamine on responding maintained by both food delivery and electric shock avoidance were determined using a multiple schedule of reinforcement in rhesus monkeys. This schedule had three components, each separated by a timeout: a fixed-ratio schedule of food delivery, a schedule of spaced responding (differential reinforcement of low rates) maintained by food delivery and a fixed-ratio schedule of shock avoidance. Control rates of responding on both ratio schedules were similar and were high relative to the low rates generated by the schedule of spaced responding. Perphenazine decreased rates on all three schedules in a dose-dependent fashion. All three psychomotor stimulants decreased food-maintained ratio responding at doses which had little effect on or increased rates of shock avoidance. Except for diethylpropion and d-amphetamine in one animal in which rates were increased, low rates of spaced responding were also decreased.

Animals↗
PubMed1977

Inhibition of apomorphine-induced hypermotility in rats by chlorpromazine, perphenazine, thioridazine and melperone.

Hypermotility in rats produced by various subcutaneous doses of apomorphine (ap) was studied. The neuroleptics chlorpromazine, perphenazine, thioridazine and melperone were administered subcutaneously 30 minutes before ap. The four neuroleptics were found to inhibit ap-induced hypermotility. When the dose of ap was increased, higher doses of the neuroleptics were required to inhibit the hypermotility. By varying the dose of chlorpromazine, thioridazine and melperone partial ap-antagonism was found, but increase of the perphenazine-dose resulted in complete ap-inhibition. Hypermotility produced by ap is presumably dependent on direct stimulation of dopamine (DA)-receptors. Neuroleptics blocking some, but not all, DA-receptors may cause no, or weak parkinsonian side effects.

Animals↗
PubMed1976

[Study of the clinical effects of sulpiride and perphenazine in 82 schizophrenic patients by the double blind method].

Our clinical and statistical evaluation of Sulpiride and Perphenazine was carried out over a 10 week period, in 82 patients of both sexes, aged 20 to 56 years. All were chronic patients with a symptomatic profile of apathy, lack of initiative but with the personality relatively well preserved in 56 patients. The daily dosage varied from 300 to 1,200 mg Sulpiride orally and 12 to 48 mg Perphenazine. The effects of therapy have been received globally and individually at the beginning, 4th, 8th, and the end of the 10th week using the B.P.R.S. modified by the clinic of Neurology and Psychiatry of the University of Hiroshima. Using "Armitage's Restricted Sequential Design", there was no significant difference between the therapeutic effects of these 2 neuroleptics. However, Sulpiride appeared more beneficial following the review during the 8th week and the 4th week.

Adult↗
PubMed1998

[Paranoid psychosis in acute intermittent porphyria treated with perphenazine].

Several drugs may induce or exacerbate symptoms in acute porphyria. This includes most psychotropic drugs, which makes the treatment of psychiatric symptoms in the porphyric patient difficult. A patient with a paranoid psychotic condition related to acute intermittent porphyria was treated with perphenazine. The use of this drug has not previously been reported in acute intermittent porphyria. Therefore, the treatment was closely monitored clinically and biochemically. No deterioration in the porphyric state was observed. However, further experience is needed before perphenazine may be considered as a drug that can be used safely in acute intermittent porphyria.

Adult↗
PubMed1976

[Pharmacokinetic profile of perphenazine enanthate].

Publications on blood kinetics, biotransformations, excretion and tissular distribution of Perphenazine and its enanthic ester were analyzed. They allowed to make the pharmacokinetic profile of Perphenazine Enanthate, a long-acting neuroleptic, and to draw some information concerning its therapeutic use.

Adult↗
PubMedDate not supplied

Effects of protriptyline and perphenazine in neurotic depressed outpatients.

A four-week comparison of protriptyline 10 mg three times a day and perphenazine 2 mg three times a day, alone and in combination, and a placebo in a group of nonpsychotic depressed outpatients showed no significant differences among any of the treatment groups after both two and four weeks, and a slight trend in favor of the placebo group. A significant positive correlation was observed between changes in hostility and changes in depression, contrary to many commonly held assumptions regarding the relationship between hostility and depression.

Adjustment Disorders↗
PubMed1993

Logarithmic transformation in bioequivalence: application with two formulations of perphenazine.

The rationale for using the logarithmic transformation on concentration-dependent pharmacokinetic parameters a priori is presented. This rationale is based on theoretical pharmacokinetic and statistical grounds, but is also applicable to the practice of physicians in dealing with variations of drug treatment within and between patients. The implications of the transformation on data analysis, specifically analysis of variance, and estimation and inference from the analysis as it pertains to bioequivalence decisions are explored. Implementation of the transformation is shown, with an example of two perphenazine formulations in a single-dose crossover study. It is concluded that the transformation has to be accepted on theoretical grounds because sample sizes are too small in bioequivalence studies and too susceptible to extreme values to state with any certainty the actual distribution of pharmacokinetic parameters or their differences within a subject.

Adolescent↗
PubMed1977

Plasma concentrations of perphenazine and its sulphoxide metabolite during continuous oral treatment.

Plasma concentrations of perphenazine (PPZ) (Trilafon) and perphenazinesulphoxide (PPZSO) were estimated during a 2-week period in 16 patients receiving peroral PPZ treatment for various psychotic disorders. The results demonstrated that the average concentration of three plasma samples was a reasonably good expression of the steady-state plasma level despite a great fluctuation in the concentration from sample to sample. Increased doses in three of the patients resulted in disproportionate increases in the plasma levels. Neurological side effects were recorded and their relation to plasma concentrations are discussed.

Administration, Oral↗
PubMed1976

High-dose treatment of rats with perphenazine enanthate.

Previously we demonstrated an approximately 20% loss of nerve cells in the basal ganglia of rats following treatment with perphenazine enanthate 3.4 mg/kg s.c. every 2nd week during 12 months. If the treatment period was only 2 or 3 months no significant differences were found.

Animals↗
PubMed1978

Effects of perphenazine enanthate injections on prolactin levels in plasma from schizophrenic women and men.

Levels of prolactin (PRL) in plasma were determined in schizophrenic women and men after i.m. injections of 50-150 mg perphenazine enanthate (PE). In both sexes PRL levels increased dose-dependently. In men the effect was significant for 2 and in women for 9 days. Biperiden treatment did not influence the effect of PE on the PRL levels. The data support the view that clinically used doses of PE induce a small but significant blockade of central dopamine receptors.

Aged↗
PubMed1992

Phenothiazines inhibit acetylcholinesterase by concentration-dependent-type kinetics. A study with trifluoperazine and perphenazine.

The properties of perphenazine (PPZ) and trifluoperazine (TFP) as fluorescent dyes were exploited to calculate their critical micellar concentrations. The relative fluorescence quantum yield of the two amphiphiles was dependent on their concentration, abruptly decreasing above 30-40 microM PPZ and 20-30 microM TFP. Evidence is presented that this phenomenon is driven by the formation of non-fluorescent drug aggregates. The type of inhibition kinetics displayed by PPZ and TFP on human erythrocyte acetylcholinesterase (AChE) was also dependent on drug concentration, turning from non-competitive to a "mixed" inhibition type at concentrations at which PPZ and TFP were demonstrated to undergo micelle formation. Results support the notion that phenothiazines may interact with AChE both as monomers and micellar aggregates, producing different inhibitory effects.

Acetylcholinesterase↗
PubMed1994

Effects of perphenazine on the metabolism of inositol phospholipids in SK-N-BE(2) human neuroblastoma cells.

Administration of myo-[3H]inositol to SK-N-BE(2) human neuroblastoma cells for 24 hr resulted in equilibrium labelling of phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2), as well as in retention of a large intracellular pool of free myo-[3H]inositol. Equilibrium labelling was no longer observed when cells were treated for 2 hr with 20 microM perphenazine (PPZ) in label-free medium; under these conditions, myo-[3H]inositol from the retained intracellular pool was incorporated into PI and PIP but not into PIP2. Analysis of water-soluble myo-[3H]inositol derivatives and inositol 1,4,5-trisphosphate mass determination indicated that PPZ did not stimulate phosphoinositide hydrolysis by phospholipase C. These results indicate that PPZ raises PI and PIP levels, whereas it is ineffective in expanding the PIP2 pool. The latter effect is not due to a concomitant synthesis and hydrolysis of this lipid.

Cell Line↗
PubMed1977

An investigation of nalorphine and perphenazine as negative reinforcers in an escape paradigm.

Rhesus monkeys were trained to self-administer morphine intravenously at dose levels sufficient to develop physical dependence. The monkeys were then trained to press a lever to escape a continuous infusion of the morphine antagonist, nalorphine. When saline was substituted for the nalorphine, escape responding extinguished. After morphine self-administration was eliminated, responding to escape from nalorphine was maintained in the postdependent monkeys, showing no difference from escape responding during morphine dependence. Finally, perphenazine was substituted for the nalorphine and the monkeys reliably escaped continuous infusions of this phenothiazine. The escape procedure appears useful for analyzing the aversive properties of drugs.

Animals↗
PubMed2005

Mitochondria and plasma membrane as targets of UVA-induced toxicity of neuroleptic drugs fluphenazine, perphenazine and thioridazine.

In order to gain insights into the mechanism of phototoxicity of the neuroleptic drugs fluphenazine, perphenazine and thioridazine in cultured cells, studies were performed with murine 3T3 fibroblasts, aimed at identifying some cellular targets responsible for photoinduced cell death and possible cytotoxic reactive species involved in the photosensitization process. 3T3 fibroblasts incubated with 5 microM drugs and irradiated with UVA light (up to 8 J/cm2) underwent cell death, the extent of which depended on light dose. Of the three drugs, fluphenazine exhibited the highest phototoxicity and 100% cell death was achieved with a light dose of 5 J/cm2. Superoxide dismutase and alpha-tocopherol exerted a dose-dependent protective effect against drug phototoxicity, whereas N-acetylcysteine failed to do so. These findings indicate that superoxide anion and other free radical intermediates, generated in lipophilic cellular environments, play a role in photoinduced toxicity. Phototreatment of drug-loaded cells induces release of the cytosolic enzyme lactate dehydrogenase and causes loss of activity of mitochondrial NADH dehydrogenase, indicating that plasma membrane and mitochondria are among the targets of the phototoxicity of these drugs.

3T3 Cells↗
PubMed2005

Application of two chemometric methods for the determination of imipramine, amitriptyline and perphenazine in content uniformity and drug dissolution studies.

Double-divisor spectra derivative and partial least squares methods were developed for content uniformity and dissolution tests in binary or ternary mixtures. The simultaneous determinations of perphenazine (PER) combined with amitriptyline hydrochloride (AMI) and/or imipramine hydrochloride (IMI) have been accomplished using the information of the absorption spectra of appropriate solutions. The double-divisor method is based on the use of the first derivative of the ratio spectrum obtained by dividing the absorption spectrum of the ternary mixture PER-AMI-IMI by a standard spectrum resulted from the addition of two of the three analytes in equal concentrations. The concentration of each component is then determined from their respective calibration graphs established by measuring the ratio derivative analytical signal at a specific wavelength. In this method, the linear determination ranges were of 3.65-18.24 microg/mL for PER, 4.32-21.60 microg/mL for AMI, and 4.83-24.19 microg/mL for IMI. The results were compared with those obtained by partial least squares multivariate calibration (PLS) method pre-treated by a wavelet compression-orthogonal signal correction (W-OSC) filter in zero-order derivative spectra. The calibration model was evaluated by internal validation (cross-validation) and by external validation over synthetic mixtures, content uniformity and dissolution tests. According to the dissolution profile test more than 95% of the three substances were dissolved within 10 min. The results from both techniques were statistically compared with each other and can be satisfactorily used for quantitative analysis and dissolution tests of multicomponent tablets.

Amitriptyline↗
PubMed1991

Extrapyramidal symptoms and their relationship to clinical efficacy under perphenazine treatment. A controlled prospective handwriting-test study in 22 acutely ill schizophrenic patients.

In order to verify the hypothesis of a strict relationship between clinical improvement and extrapyramidal side-effects, especially micrographia, twenty-two acutely ill schizophrenics were treated with perphenazine in a controlled prospective 28-day trial. During the study period, psychopathometric data, prolactin plasma levels, and handwriting samples were collected. According to the remission criteria fixed before the study began (both BPRS less than or equal to 25 and GAS greater than or equal to 80 points), 45.5% (10/22) of the total patient sample were classified as treatment responders. Handwriting tests were quantified in 21 patients. "Positive" handwriting results, i.e., a reduction of at least 13% in the overall area of 50% or more of the handwriting samples collected during the trial, were demonstrable in three of nine responders (33%) and nine of twelve nonresponders (75%). These results show that there is no positive correlation between clinical response and reduction in handwriting area. Consequently, the handwriting test is unable to predict clinical response. It is only one of a number of parameters with which to monitor the neurological side-effects of neuroleptic treatment. Outcome parameters show that psychopathological remission can be achieved with low neuroleptic dosages and few or virtually no extrapyramidal side-effects.

Acute Disease↗
PubMed1999

Perphenazine-induced hiccups.

Hiccup is a spasmodic, involuntary contraction of the inspiratory muscles, associated with delayed and abrupt glottic closure causing a peculiar sound (Launois et al., 1993). A number of medical conditions are known to cause persistent and intractable hiccups. Among the drugs reported to induce hiccups, Thompson et al. stated that corticosteroids and benzodiazepines are the drug classes most frequently associated with the development of hiccups (Thompson and Landry, 1997). Antidopaminergic agents such as chlorpromazine and haloperidol are the preferred drugs used for the treatment of chronic hiccups (Launois et al., 1993). We report a case of severe hiccups occurring in association with the administration of perphenazine, which is a dopamine antagonist. To the best of our knowledge, this is the first report of hiccups occurring as a side effect of antidopaminergic drugs.

Adult↗