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PubMed1986

Yohimbine potentiates the anticataleptic action of clonidine against perphenazine-induced catalepsy in rats.

The modulatory role of clonidine and yohimbine on the perphenazine-induced catalepsy was studied in rats. Perphenazine (5 mg/kg) produced severe catalepsy which lasted for more than 4 hr. Clonidine (50 micrograms/kg), an alpha 2-agonist, pretreatment offered protection against perphenazine-induced catalepsy. On the other hand yohimbine (5 mg/kg), an alpha 2-antagonist, pretreatment not only showed per se protective action but also potentiated the effects of clonidine against perphenazine-induced catalepsy. Yohimbine also potentiated the protective action of quipazine, a serotonin agonist. The protective effect of yohimbine is explained on the basis of its serotoninergic action.

Animals↗
PubMed1977

Reinforcing properties of perphenazine, haloperidol and amitryptiline in rhesus monkeys.

Possible negative reinforcing effects of perphenazine, haloperidol and amitryptiline were studied in rhesus monkeys previously trained to avoid electric shock by responding. Responding extinguished a light associated with an intravenous drug infusion scheduled to occur 30 seconds after the light was switched on. A response occurring when the light was on switched the light off for a period of 1 minute (time-out period). a response during the infusion terminated the infusion. Under these conditions, the monkeys tolerated a large number of saline infusions. Saline was replaced by different doses of perphenazine, haloperidol and amitryptiline, each for 12 successive daily 2-hour sessions. Infusions of perphenazine (0.50-1.6 microng/kg) and to a lesser extent infusions of haloperidol (2.5 microng/kg) generated and maintained responding. Most of the infusions of amitryptiline in the dose range of 1.0 to 10.0 microng/kg were tolerated. Haloperidol and perphenazine in doses higher than 10.0 micmitryptiline (500-3000 microng/kg i.v.) had no influence on shock avoidance behavior. Positive reinforcing effects of these compounds were studied in a group of monkeys trained to respond under a 10 response fixed ratio of intravenous infusions of codeine. None of the three compounds maintained responding previously engendered by codeine.

Amitriptyline↗
PubMed1995

Comparison of the kinetic interactions of the neuroleptics perphenazine and zuclopenthixol with tricyclic antidepressives.

Using data from a therapeutic drug monitoring database, kinetic interactions between the neuroleptics zuclopenthixol and perphenazine and tricyclic antidepressives were studied. Out of 290 patients monitored for amitriptyline and 611 patients monitored for nortriptyline, 77 patients were comedicated with perphenazine and 50 patients with zuclopenthixol. Comedication with perphenazine increased the median steady-state serum concentration to daily dose ratio (C/D) of nortriptyline by 30-45%, whereas the median C/D of amitriptyline was unaffected. On the contrary, median C/D values of nortriptyline and amitriptyline were not significantly influenced by comedication with zuclopenthixol. Thus, in accordance with previous studies, perphenazine increases the concentration of tricyclic antidepressives to a moderate extent. Zuclopenthixol, on the other hand, does not exert any impact under routine therapeutic drug monitoring, even though the drug is known to partly depend on metabolism by the isozyme cytochrome P450 2D6.

Adolescent↗
PubMed1976

The effect of perphenazine treatment during the organogenesis in rats.

The teratogenic effect of perphenazine was studied in closed-bred Wistar rats. Rats were given the substance orally continuously on days 7 to 14 of pregnancy, or as a single dose on one of days 9-15. The doses were considerably higher than the specific neuroleptic doses of perphenazine (20-150 mg/kg). The fetal mortality and malformation rates were significantly higher in the perphenazine-treated groups than in the controls. The results were compared with the earlier results of methophenazine treatment. Perphenazine was found to be more toxic for rat embryos than methophenazine.

Abnormalities, Drug-Induced↗
PubMed1977

High-performance liquid chromatographic determination of perphenazine and amitriptyline hydrochloride in two-component tablet formulations.

A rapid, precise, and accurate high-performance liquid chromatographic procedure is presented for the simultaneous determination of perphenazine and amitriptyline hydrochloride in two-component tablet formulations. An aliquot of a methanolic extract of the tablet, containing trifluoperazine hydrochloride as an internal standard, is chromatographed on a nitrile bonded phase microparticulate column using a 0.005 M ammonium acetate-methanol (20:80) mobile phase. Quantitation is by peak area. The relative standard deviations for the procedure are 0.34 and 0.54% for the simultaneous determination of perphenazine and amitriptyline, respectively. Eight commercial tablet formulations were analyzed and found to contain 96.5-101.5 and 96.5-103.3% of the labeled amounts of perphenazine and amitriptyline hydrochloride, respectively.

Amitriptyline↗
PubMed1985

Therapeutic advantages of monitoring plasma concentrations of perphenazine in clinical practice.

Two hundred and twenty-eight acute paranoid psychotic in-patients received continuous treatment with perphenazine for a period of at least 5 weeks, before blood samples were taken to determine perphenazine plasma levels and conclusions regarding therapeutic efficacy and motor side effects. Patients with plasma concentrations within the range of 2-6 nmol/l showed an excellent antipsychotic response, concomitantly with a low incidence of extrapyramidal side effects. However, patients with plasma levels below or above this range either demonstrated a poor therapeutic response or a high degree of side effects respectively. The results indicate that with increasing age significantly lower doses of perphenazine are required to ensure an optimal clinical response. No difference, however, was seen between sexes with regard to dose response.

Adolescent↗
PubMed2006

Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients.

RATIONALE: Perphenazine, a classical antipsychotic drug, has the potential to induce extrapyramidal side effects (EPS). Dopaminergic and serotonergic pathways are involved in the therapeutic and adverse effects of the drug. OBJECTIVES: To evaluate the impact of polymorphisms in the dopamine D(2) and D(3) and serotonin 2A and 2C receptor genes (DRD2, DRD3, HTR2A, and HTR2C) on short-term effects of perphenazine monotherapy in schizophrenic patients. MATERIALS AND METHODS: Forty-seven Estonian inpatients were evaluated before and after 4-6 weeks of treatment by Simpson-Angus rating scale, Barnes scale, and Positive and Negative Symptom Scale. Genotyping was performed for common DRD2, DRD3, HTR2A, and HTR2C gene polymorphisms, previously reported to influence receptor expression and/or function. RESULTS: Most of the patients (n = 37) responded to the treatment and no significant association was observed between the polymorphisms and antipsychotic response. The 102C allele of HTR2A and the -697C and 23Ser alleles of HTR2C were more frequent among patients with EPS (n = 25) compared to patients without EPS (n = 22) (p = 0.02, 0.01, and 0.02, respectively). The difference between patients with and without EPS in variant allele frequencies remained significant after multiple model analyses including age, gender, and duration of antipsychotic treatment as covariants. There was no significant association between EPS occurrence and polymorphisms in the DRD2 and DRD3 genes. CONCLUSIONS: An association was observed between polymorphisms in HTR2A and HTR2C genes and occurrence of acute EPS in schizophrenic patients treated with perphenazine monotherapy. Larger study populations are needed to confirm our findings.

Adolescent↗
PubMed1992

Lithium in combination with perphenazine: effect on plasma monoamine metabolites.

The addition of lithium to perphenazine altered the pattern of plasma homovanillic acid (HVA) during the course of treatment for acute psychosis. In the perphenazine-treated group plasma HVA declined significantly by days 7-9 of treatment, whereas in the perphenazine-plus-lithium group plasma HVA tended to increase. The pattern for plasma methoxyhydroxyphenethyl-glycol (MHPG) was not significantly different for the two groups. The addition of lithium to a neuroleptic may enhance the metabolism of dopamine.

Adult↗
PubMedDate not supplied

Comparative effects of prolactin, perphenazine and reserpine on non-arteriosclerotic (virgin) vs arteriosclerotic (breeder) rats.

Non-arteriosclerotic, virgin and arteriosclerotic breeder rats were subjected to chronic treatment with prolactin or prolactin-releasing drugs such as perphenazine and reserpine for 12 weeks. Males and females responded to the prolactin as evidenced by increased milk secretion, adrenal hyperplasia and thymus gland involution. Although the prolactin- and reserpine-treated animals gained weight and manifested pituitary gland basophilia, the perphenazine-treated animals showed considerable loss of body weight as well as involution of the pituitary gland, ovaries and testes, suggesting a condition of induced hypopituitarism. Chronic treatment with prolactin, both directly and indirectly, caused uniform increases in serum enzymes, e.g., CPK, SGOT, SGPT and LDH, lipids, e.g., triglycerides, free fatty acids and cholesterol, glucose and BUN. Corticosterone production was enhanced by prolactin, reduced by perphenazine and unaffected by reserpine. Prolactin did not induce any arterial disease in the arteriosclerosis-resistant, virgin rats but it did cause eracerbation of the usual severity of arteriosclerosis in the hilar renal arteries of the arteries sclerosis-prone, breeder rats as well as an increased incidence of "old" and "new" foci of myocardial necrosis, characteristically found in breeder rats. It is suggested that hypothalamic control of prolactin as well as ACTH release may play a role in the spontaneous arteriosclerosis which develops in repeatedly-bred, male and female rats.

Alanine Transaminase↗
PubMed1979

Metabolic interaction between amitriptyline and perphenazine in psychiatric patients.

1. Steady-state plasma level samples of sixty-five schizophrenic patients from two psychiatric hospitals assigned to three treatment groups (amitriptyline 150 mg/day, perphenazine 20 mg/day and a combination of amitriptyline and perphenazine at 150 mg and 20 mg/day) were assayed for amitriptyline (AT), endogenous nortriptyline (NT) and perphenazine (PPZ) using gas-liquid chromatography. 2. Results reveal that AT and NT levels are independent of sex and hospital environment. 3. PPZ significantly increased the steady-state NT plasma levels, probably through inhibition of the hydroxylation biotransformation pathway, but had no effect on AT levels, thus indicating that PPZ has no influence on the desmethylation pathway, or alternatively, the hydroxylation of AT.

Adult↗
PubMed1996

Steady-state serum concentrations of the neuroleptic perphenazine in relation to CYP2D6 genetic polymorphism.

Steady-state serum concentration to dose ratios of the neuroleptic agent perphenazine were related to CYP2D6 metabolizer status for 96 psychiatric inpatients: 88 extensive metabolizers and eight poor metabolizers. The median concentration per dose of the poor metabolizer group (0.195 nmol/L per milligram) was about twice the median (0.098 nmol/L per milligram) of the 56 extensive metabolizers without interacting medicine (p < 0.01). The rest of the extensive metabolizers (n = 32), who were comedicated with drugs that compete with perphenazine for metabolism by CYP2D6, had an intermediate median value of 0.140 nmol/L per milligram. The range of concentration/dose values for the total extensive metabolizer group extended from 0.025 to 0.688 nmol/L per milligram, that is, an almost thirtyfold variation. The concentration/dose range of the eight poor metabolizer subjects was 0.096 to 0.750 nmol/L per milligram. Serum levels not corrected for dose overlapped to a large degree among the groups, with a total range from 0.5 to 12 nmol/L. This study points toward a limited information value of CYP2D6 genotyping in the context of therapeutic drug monitoring of perphenazine.

Adolescent↗
PubMed1975

Determination of perphenazine and its sulphoxide metabolite in human plasma after therapeutic doses by gas chromatography.

A gas chromatographic method for the determination of perphenazine (Tri-lafon) and its main metabolite in human plasma, perphenazine sulphoxide, has been developed. The procedure involves the use of an electron capture detector and permits the determination of the drug and its metabolite at concentrations down to 0.2 mug/l. This is sufficient for analyzing plasma from patients on ordinary treatment with perphenazine. Tests for specificity revealed no interference by nortriptyline or biperidine.

Biotransformation↗
PubMed1989

Disposition of perphenazine is related to polymorphic debrisoquin hydroxylation in human beings.

The pharmacokinetics of a single oral dose of 6 mg perphenazine was studied in a group of six slow and six rapid hydroxylators of debrisoquin. Peak serum concentrations of perphenazine were significantly higher in slow hydroxylators than they were in rapid hydroxylators (2.4 +/- 0.6 versus 0.7 +/- 0.3 nmol/L, p less than 0.001). The AUC(0-12) was also higher in slow hydroxylators than it was in rapid hydroxylators (18.5 +/- 6.2 versus 4.5 +/- 2.5 nmol.L-1.hr, p less than 0.001). The data suggest that the disposition of the antipsychotic drug perphenazine covaries with polymorphic debrisoquin hydroxylation.

Administration, Oral↗
PubMed1987

Zuclopenthixol and perphenazine in patients with acute psychotic states. A double-blind multicentre study.

Fifty-four patients with acute psychotic states were included in a double-blind multicentre study of zuclopenthixol and perphenazine given orally. Fourteen patients had not received test preparations for a minimum of 3 weeks as stated in the protocol, and were excluded. The remaining 40 patients received the test preparations for 3 to 12 weeks, with an average of 49 days for patients receiving zuclopenthixol and 45 days for patients receiving perphenazine. Clinical evaluations were done at baseline and at weeks 1, 2, 4, 6, 8, and 12 including the CGI, a CPRS subscale for schizophrenia, and the UKU Side Effects Rating Scale. The patients received on average 37 mg zuclopenthixol or 30 mg perphenazine daily. Statistically, significant reductions on the CGI, severity of illness, and on the CPRS (total score) were found for both drugs when comparing baseline with later scores. No significant differences between the drugs were found. It was also impossible to demonstrate a difference in clinical profile between the two drugs on the basis of the single items on the CPRS. Although small differences between the two drugs were found, as regards number and type of side effects, it is concluded that the pattern of side effects was almost identical in the two treatment groups.

Clopenthixol↗
PubMed1981

Radioimmunoassay for perphenazine in human plasma.

1 A new sensitive, specific and rapid radioimmunoassay procedure for the determination of plasma concentrations of the neuroleptic drug perphenazine is described. 2 The antiserum developed for perphenazine did not cross-react with most of the major metabolites of perphenazine nor the tricyclic antidepressants and antianxiety agents commonly co-administered with the drug. 3 The assay, based on the above antiserum, enabled the quantitation of 50 pg of the drug in 200 microliters of plasma with a coefficient of variation of about 8% and therefore should be applicable for single dose pharmacokinetic studies, as well as therapeutic monitoring of the drug in patients.

Animals↗
PubMed2002

Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients.

OBJECTIVE: Until recently, conventional antipsychotics were the standard pharmacotherapy for psychosis and behavioral disturbances associated with dementia. This double-blind, placebo-controlled study compared the acute efficacy of the selective serotonin reuptake inhibitor citalopram and the neuroleptic perphenazine with placebo for the treatment of psychosis and behavioral disturbances in nondepressed patients with dementia. METHOD: Eighty-five hospitalized patients with at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions) were randomly assigned to receive either citalopram, perphenazine, or placebo under double-blind conditions for up to 17 days. RESULTS: Patients treated with citalopram or perphenazine showed statistically significant improvement on several Neurobehavioral Rating Scale factor scores. Compared to those receiving placebo, only patients treated with citalopram showed significantly greater improvement in their total Neurobehavioral Rating Scale score as well as in the scores for the agitation/aggression and lability/tension factors. Side effect scores were similar among the three treatment groups. CONCLUSIONS: Citalopram was found to be more efficacious than placebo in the short-term hospital treatment of psychotic symptoms and behavioral disturbances in nondepressed, demented patients.

Aged↗
PubMed1976

Clozapine versus perphenazine: the value of the biochemical mode of action of neuroleptics in predicting their therapeutic activity.

The chemical structure of a neuroleptic does not relaibly predict the exact profile of its therapeutic action. We considered the question whether the biochemical action of a neuroleptic, and specifically the ratio between DA-receptor block and NA-receptor block, might have a higher predictive value in this respect. In this context we carried out a double-blind study of the therapeutic value of clozapine and perphenazine in acute psychoses of varying symptomatology anc aetiology. There are strong indications that clozapine has only a slight inhibitory effect on transmission in central DA-ergic neurons, but markedly inhibits transmission in central NA-ergic neurons, and that the reverse applies to perphenazine. In view of these data we expected perphenazine to be a stronger antipsychotic and a weaker sedative than clozapine, and vice versa. The plausibility of this hypothesis was demonstrated. Partly also on the basis of earlier research, we concluded that the biochemical action of a neuroleptic is a more faithful predictor of its therapeutic action profile than the chemical structure.

Adult↗
PubMed1975

Prolactin and growth hormone levels in different inbred strains of mice: patterns in association with estrous cycle, time of day, and perphenazine stimulation.

These experiments were designed to compare prolactin (PRL) and growth hormone (GH) secretion in strains of mice with varying incidences of mammary tumors. In addition to the basal levels, PRL concentrations were compared after stimulation with perphenazine. Although pituitary concentrations of PRL and pituitary serum concentrations of GH appeared to be generally higher in strains with high incidence of mammary tumors, basal PRL levels in single decapitate serum samples seemed to have little correlation with the incidence of mammary tumors in different strains. However, PRL concentrations in sera after perphenazine injection followed a pattern characteristic of the mammary tumor incidence rate of the strain: C3H/St and CBA/St--the two high-incidence strains--had lower levels of PRL; C57BL/St and BALB/cST--the two low-incidence strains--had higher levels; and DBA/2St--the medium-incidence strain--had an intermediate level. PRL contents of the pituitary glands were depleted virtually equally in all strains except the BALB/cSt. These results suggested that the rate of metabolism of PRL in strains with high incidence of mammary tumors may be faster than in those with low incidences. Perphenazine had no influence on GH secretion in most mice. The strain-specific differences in PRL and GH concentrations were usually present even during cyclical and diurnal fluctuations. Serum PRL and GH levels were generally higher during the follicular phase and lower during the luteal phase of the estrous cycle in both C3H/St and C57BL/St strains. There were signs of episodic secretion of PRL together with evidences of circadian periodicity in the secretion of PRL and GH in mice of both strains. The levels of GH were usually high during the morning hours of those of PRL high during the evening hours. The data show a high degree of specificity in the secretion of PRL and GH im mice of different inbred strains, and it is possible that these strain-specific differences may be an important factor in the development of mammary tumors.

Animals↗