Amount Of Chlorpromazine Research Articles

The in vitro biokinetics of chlorpromazine and diazepam in aggregating rat brain cell cultures after repeated exposure

Neurotoxic effects of compounds can be tested in vitro using cell systems. One example is aggregating rat brain cell cultures. For the extrapolation of in vitro data to the in vivo situation, it is important to take the biokinetics of the test compound into account. In addition, the exposure in vivo is often for a longer period of time; therefore, it is crucial to incorporate this into in vitro assays as well. In this study, aggregating rat brain cell cultures were exposed to chlorpromazine (CPZ) and diazepam (DZP) for 12-days with repeated exposure. Samples were taken from the stocks, test media, cell culture media and cells at specific time points on the first and last exposure day. These samples were analysed by HPLC-UV. The amount of CPZ in the medium decreased over time, whereas the amount in the cells showed an increase. Accumulation of CPZ in the cells was seen over the 12-day repeated exposure. The amount of DZP in the medium remained stable over time and only up to 2% of DZP added was found in the cells. Different biokinetic behaviour was found for CPZ and DZP. Possible explanations are differences in uptake into the cells or efflux out of the cells. The decrease of CPZ in the medium versus the stable amount of DZP results in differences in exposure concentrations over time, which should be taken into account when interpreting in vitro effect data.

Anesthetic management with eptazocine hydrobromide in patients receiving long-term antipsychotic medication.

We evaluated the usefulness of eptazocine hydrobromide as an adjuvant in patients receiving antipsychotics for long periods. Patients anesthetized with enflurane alone (enflurane group, n = 11), were compared with those anesthetized with enflurane and eptazocine hydrobromide 1 mg.kg(-1) (eptazocine group, n = 10). The mean daily dose of the antipsychotics, converted into the amount of chlorpromazine, was 345 mg in the eptazocine group and 366 mg in the enflurane group. The duration of antipsychotic medication was 14 years in the eptazocine group and 17 years in the enflurane group. The maintenance concentration of enflurane was 0.37% in the eptazocine group and 0.67% in the enflurane group, being significantly lower in the former group. The interval between the termination of operation and removal of the endotracheal tube was slightly shorter in the eptazocine group. The discriminant function of circulatory stability obtained from the measurement of systolic blood pressure and heart rate during anesthesia in the eptazocine group was 481, being significantly lower than 539 in the enflurane group. Both absolute and relative instabilities of systolic blood pressure and heart rate were slightly smaller in the eptazocine group. No side effects associated with eptazocine hydrobromide administration were observed. These results suggest the safety and usefulness of this analgesic in the anesthetic management of patients receiving long-term antipsychotic medication.

Interaction between Chlorpromazine and Radiation Damage to Human Erythrocyte Membrane

MISHRA, K. P., SRINIVASAN, V. T., AND SINGH, B. B. Interaction between Chlorpromazine and Radiation Damage to Human Erythrocyte Membrane. Radiat. Res. 88, 413-419 (1981). The effect of y irradiation on human erythrocytes and the modification of this by chlorpromazine (CPZ) have been investigated, the extent of hemolysis induced being taken as a criterion of damage. Cells irradiated under isotonic conditions for doses up to 150 krad did not hemolyze to any significant extent when measured within a few minutes of irradiation. The hemolysis gradually increased on postirradiation incubation, and eventually complete hemolysis occurred suddenly within a span of 2 to 3 hr. The time taken for complete hemolysis depended on the radiation dose. The stability of these irradiated cells in 0.45% sodium chloride solution decreased with postirradiation incubation. The extent of hypotonic hemolysis was found to be linearly dependent on the radiaiton dose. Under isotonic conditions, 0.25 mM of CPZ did not induce any significant hemolysis while 0.5 mM of CPZ caused complete hemolysis in about 12 hr. However, treatment of irradiated cells with 0.25 mM CPZ showed a synergistic effect. Although the amount of CPZ bound to the irradiated cells did not change with dose, the extent of drug-induced hemolysis increased with dose. The present results may partly explain the synergistic effect of CPZ and radiation on tumors.

Effect of Antiparkinsonian Medication on Plasma Levels of Chlorpromazine

Twenty-one chronic schizophrenics were stabilized with chlorpromazine therapy at their therapeutic dosage for one month. Trihexyphenidyl hydrochloride or identical placebo was then added according to a double-blind, split crossover design. The duration of each half of the crossover was 15 days. Steady state blood samples were drawn three times weekly during the experimental period and the amount of chlorpromazine was determined. The results indicated there were no differences in the levels obtained between the trihexyphenidyl and the placebo phases. A two-hour postdrug blood sample was also drawn at the end of each phase and again, there were no differences between the two conditions. The importance of these results is discussed.

A mass fragmentographic method for the determination of chlorpromazine and two of its active metabolites in human plasma and CSF

A mass fragmentographic method for the quantitation of chlorpromazine (CPZ), mono-demethyl-chlorpromazine (nor1-CPZ), and 7-hydroxy-chlorpromazine (7-OH-CPZ) in plasma, cerebrospinal fluid, and tissues has been developed. The deuterated analogues of the compounds are used as internal standards. The high specificity was ascertained by multiple ion determination. The experimental error is below 10%. The sensitivity allows determination of sub ng quantities of CPZ per ml cerebrospinal fluid. The method has been applied to the analysis of drug concentrations in plasma and cerebrospinal fluid (CSF) of chlorpromazine-treated patients. The amount of CPZ in CSF was about 3% of the plasma level. The CPZ levels in plasma and CSF were significantly correlated.

Scorpion Bite Treatment With Chlorpromazine

To the Editor:— A few years ago, while working in Arizona on Indian reservations for the Public Health Service, I treated scorpion bites on three occasions. I learned from my colleagues that there was little to do for these patients but sedate them with barbiturates and observe them for a day or two if they seemed to have very toxic effects. This required in some cases huge or repeated doses of barbiturates and could take hours of observation. During the treatment of my first case in a 4-year-old girl, she appeared to be psychotic and I administered a small amount of chlorpromazine, intravenously. This was after approximately three hours of unsuccessful atempts at sedation with barbiturate, a total amount of a fantastic 160 mg of phenobarbital. The chlorpromazine yielded dramatic results within minutes. Subsequently I treated two similar reactions in 8- and 10-year-old boys with chlorpromazine intramuscularly with the same

Total dosage of chlorpromazine and ocular opacities.

patients for a collaborative drug study, we found that 20 patients had the fine opacities of the anterior lens capsule and corneal endothelium that have recently been reported as being associated with prolonged phenothiazine administration(2, 3, 5, 6). None of the patients showed any loss of visual acuity that could be attributed to the opacities. The medication histories of these 20 patients were compared with those of 20 patients matched by age and sex, but who did not have ocular changes. This paper reports the relationship of the lens and corneal endothelial opacities to the total amount of chlorpromazine (Thorazine) received by the two

On the influencing of food intake by psychotropic drugs

The effects of 16 psychotropic drugs on food intake and body weight were studied in female Wistar rats under carefully controlled conditions. After 3 days of placebo treatment the drugs were administered orally 1 hr prior to a 12-hours-per-day feeding period for at least 3 further days. Normal daily feed consumption averaged 6.11 g/100 g BW. Haloperidol, reserpine, chlorpromazine, chlorprothixene, promethazine, azacyclonol, imipramine, and amitriptyline in appropriate doses all reduced both food intake and body weight, but there were marked differences in activity. Small amounts of chlorpromazine may even stimulate feeding behaviour. Chlorpromazine sulfoxide was without influence. The central stimulant Tradon® evoked anorexia whereas only short-lasting anorexigenic effects if any were observed following the administration of either 2-diethylamino-4-oxo-5-phenyl-oxazoline or pipradol. On the other hand chlordiazepoxide, phenobarbital, and to some extent oxazepam caused the animals to increase their feed consumption and to gain weight. The results are discussed with regard to clinical reports of appetite and weight changes due to psychotropic drugs.

UNCOUPLERS OF OXIDATIVE PHOSPHORYLATION AND TERATOGENIC ACTIVITY OF INSULIN.

TREATMENT with insulin has well-established teratogenic effects in chick development. When administered during the earliest stages of incubation (first 2 days), it is responsible for the occurrence of rumplessness (chiefly absence of the tail vertebrae), whereas somewhat later (4th or 5th) day) it leads to a syndrome of micromelia and abnormalities of the beak (namely, a shortened upper beak or parrot beak). During these later stages, but not in the early ones, the teratogenic activity of insulin is strikingly exaggerated by the simultaneous administration of chlorpromazine1. The amounts of chlorpromazine which produce this effect were non-teratogenic and only moderately toxic if given alone.

MOTHER'S MILK AND CHLORPROMAZINE

The amount of chlorpromazine was measured in the breast milk of a lactating psychotic woman after 1200 mg. Cpz. was given in a single oral dose. The microgram amounts found were probably insignificant physiologically. Our study suggests that babies of mothers receiving large doses of chlorpromazine can be safely breast-fed.

Effects of chlorpromazine on acquisition and extinction of a conditioned response in mice.

Mice acquired a tone-shock association under conditions of saline injections, or an injection of 1.5 mgm./kgm. or 4.5 mgm./kgm. of chlorpromazine. Five days later the Ss were tested for retention of the response by being given extinction trials. Each of the three groups were divided and received either a saline injection or an injection of 1.5 mgm./ kgm. chlorpromazine just prior to extinction testing. A significant linear dose response function was obtained between amount of chlorpromazine injected during acquisition and performance under extinction, with the saline group requiring the greatest number of trials to extinguish. The presence or absence of chlorpromazine during extinction did not affect performance, nor was there any interaction between drug levels during acquisition and drug levels during extinction.

Inhibitory action of chlorpromazine on the oxidation of d-amino-acid in the diencephalon part of the brain.

AMONG several substances examined in our laboratory for their influence on the activity of D-amino-acid oxidase, chlorpromazine (N-(3′-dimethylaminopropyl)-3-chlorophenothiazine hydrochloride) was found to be a powerful inhibitor of this enzyme. The inhibitory mechanism was investigated using a purified oxidase enzyme system and Warburg manometer, and the kinetic study carried out. D-Amino-acid oxidase protein was prepared from hog kidney by the method of Negelein and Bromel1. Each enzyme system consisted of apo-enzyme (protein E), 1.6 × 10−7 mole of flavin adenine dinucleotide prepared by the method of Yagi et al. 2, 6.25 × 10−2 mole of D-alanine. Amounts of chlorpromazine (supplied by Rhone-Poulenc-Specia) ranging from 2 × 10−5 to 4 × 10−6 mole were added to these enzyme systems.