Inhibitory Effect Of Chlorpromazine Research Articles

Immunomodulatory properties of splenocytes treated with chlorpromazine in experimental aggression

Aggressive behavior is considered to be as one of the central symptoms of many neuropsychiatric disorders. It is a serious medical and biological problem associated both with high frequency and severity of manifestations and lack of selective correction means. The purpose of this study was to evaluate the functional phenotype of immune cells treated with chlorpromazine in aggressive animals in vitro, as well as the effect of transplantation of these cells on syngeneic aggressive recipient’s immune cells functional activity. Aggressive behavior was formed in active mice as a result of repeated experience of victories in agonistic interactions with animals with a submissive partner. Further, aggressive animals were isolated into individual cells and used as donors and recipients of immune cells. Immune cells were obtained under sterile conditions from suspension of spleen cells precultured with chlorpromazine. The level of spontaneous and mitogen-induced cell proliferation was assessed using a standard method of radioactive label incorporation. The quantitative content of cytokines in samples of treated with chlorpromazine cell cultures supernatant was determined by enzyme immunoassay using appropriate test systems. Further aggressive syngeneic recipients were intravenously injected with splenocytes precultured with chlorpromazine. The control group of animals was injected with splenocytes precultured under similar conditions, without the chlorpromazine addition. The recipients were assessed for the spleen cells proliferative activity and the intensity of humoral and cellular immune response using standard methods, by the number of antibody-forming spleen cells and severity of a delayed-type hypersensitivity reaction in response to T-dependent antigen introduction. It was found that treatment with chlorpromazine in vitro suppressed mitogen-stimulated proliferation of splenocytes in aggressive mice, without changing of spontaneous proliferation. It was also accompanied by some cytokines production decrease: IL-6, IL-2 and IFNã. When studying the humoral and cellular immune response intensity in aggressive recipients after transplantation of donor’s syngeneic splenocytes treated with chlorpromazine, a decrease in the intensity of humoral immune response was recorded. Transplantation of donor’s splenocytes treated with chlorpromazine was also accompanied by a decrease in spontaneous and mitogen-stimulated proliferation of splenocytes from aggressive recipients. Thus, the obtained data indicate the inhibitory effect of chlorpromazine on immune cell’s functional activity in aggressive mice, as well as the positive immunomodulatory effect of chlorpromazine-treated immune cells transplantation at aggressive behavior in experimental animals.

PELP1 Suppression Inhibits Gastric Cancer Through Downregulation of c-Src-PI3K-ERK Pathway.

Background: Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a co-activator of estrogen receptors alpha, was confirmed to be directly associated with the oncogenic process of multiple cancers, especially hormone-dependent cancers. The purpose of our research was to explore the biological function, clinical significance, and therapeutic targeted value of PELP1 in gastric cancer (GC).Methods: The expression status of PELP1 in GC cell lines or tissues was analyzed through bioinformatics data mining. Thirty-six GC tissue chip was applied to demonstrate the results of bioinformatics data mining assayed by immunohistochemical method. The expression status of PELP1 in GC cell lines was also analyzed using western blot. Correlation analysis between PELP1 expression and clinicopathological parameter was performed. Kaplan-Meier survival analysis was applied to analyze the relationship between PELP1 expression and total survival time. Three pairs of siRNA were designed to silence the expression of PELP1 in GC. After PELP1 was silenced by siRNA or activated by saRNA, the growth, plate colony formation, migration and invasion ability of the GC cell or normal gastric epithelium cell line was tested in vitro. Cell cycle was tested by flow cytometry. Nude mice xenograft experiment was performed after PELP1 was silenced. The downstream molecular pathway regulated by PELP1 was explored. Molecular docking tool was applied to combine chlorpromazine with PELP1. The inhibitory effect of chlorpromazine in GC was assayed, then it was tested whether PELP1 was a therapeutic target of chlorpromazine in GC.Results: PELP1 expression was elevated in GC cell lines and clinical GC tissue samples. PELP1 silence by siRNA compromised the malignant traits of GC. PELP1 expression positively correlated with tumor invasion depth, lymph node metastasis, tissue grade, TNM stage, but had no correlation with patient age, sex, tumor size, and tumor numbers. Kaplan-Meier survival analysis revealed high PELP1 expression had a shorter survival period in GC patients after follow-up. Q-PCR and western blot revealed PELP1 suppression in GC decreased expression of the c-Src-PI3K-ERK pathway. It was also implied that chlorpromazine (CPZ) can inhibit the malignant traits of GC and downregulate the expression of PELP1.Conclusions: In a word, PELP1 is an oncogene in gastric cancer and c-Src-PI3K-ERK pathway activation may be responsible for its tumorigenesis, PELP1 may be a potential therapeutic target of chlorpromazine in GC.

A Potential Therapeutic Target RNA-binding Protein, Arid5a for the Treatment of Inflammatory Disease Associated with Aberrant Cytokine Expression.

Infection, tissue damage and aging can cause inflammation with high levels of inflammatory cytokines. Overproduction of inflammatory cytokines often leads to systemic inflammatory response syndrome (SIRS), severe sepsis, and septic shock. However, prominent therapeutic targets have not been found, although the incidence of sepsis is likely to increase annually. Our recent studies indicate that some RNA-binding proteins, which control gene expression of inflammatory cytokines at the post-transcriptional level, may play a critical role in inflammatory diseases such as sepsis. 1) One of the RNA-binding proteins, AT-rich interactive domain-containing 5a (Arid5a) promotes cytokine production through control of mRNA half-lives of pro-inflammatory molecules such as IL-6, STAT3, T-bet, and OX40 in activated macrophages and T cells. Arid5a KO mice are refractory to endotoxin shock, bleomycininduced lung injury, and inflammatory autoimmune disease. 2) Chlorpromazine (CPZ), which is recognized as a psychotic drug, impairs post-transcriptional gene expression of Il6 in LPS-stimulated macrophages: CPZ inhibits the binding activity of Arid5a to the 3'UTR of Il6 mRNA, thereby destabilizing Il6 mRNA possibly through suppression of Arid5a expression. 3) CPZ has strong suppressive effects on cytokine production such as TNF-α in vivo. Mice with treatment of CPZ are resistant to lipopolysaccharide (LPS)-induced shock. Thus, Arid5a contributes to the activation of macrophages and T cells through positive control of mRNA half-lives of inflammatory cytokines and its related molecules, which might lead to cytokine storm. Interestingly, Arid5a was identified from an inhibitory effect of CPZ on IL-6 production in macrophages activated by LPS. Therefore, CPZ derivatives or Arid5a inhibitors may have a potential to suppress severe sepsis through control of post-transcriptional gene expression.

P079 ARID5a is an IL-6 mRNA stability protein. Chlorpromazine mediates its inhibitory effect on IL-6 production in macrophages through inhibition of ARID5A expression

Introduction Our previous study showed that chlorpromazine (CPZ), an anti-histamine therapeutic, inhibits LPS-induced IL-6 but not TNF-α production in macrophages [1] . In the current study, we show that CPZ is an inhibitor of LPS-induced IL-6 but not TNF-α mRNA stability. Since the 3′-untranslated region (3′-UTR) is important for the regulation of IL-6 mRNA stability, we examined whether CPZ affects the activity of RNA stabilizing proteins on AU-rich IL-6 3′-UTR mRNA. Here we identified a novel IL-6 mRNA stability protein, Arid5a. The Arid (AT-rich interactive domain) family of proteins have been previously demonstrated to be involved in the control of differentiation, tissue-specific gene expression and proliferation control [2] . In particular Arid5a was shown to be involved in chondrocyte-specific gene transcription [3] . In this study, we report a novel function for Arid5a on the stabilization of IL-6 mRNA. Methods For knockdown of Arid5a gene expression we employed siRNA technology. Levels of IL-6 and TNF-alpha protein in RAW 264 macrophage cell supernatants following transfection of siRNA control or ARID5a, were determined by ELISA. IL-6 and TNF-alpha mRNA stability was determined by real-time PCR. Interaction of ARID5a with the IL-6 3′-UTR was examined by mass spectrometry (LC-MS/MS). Results We found that Arid5a is induced by LPS stimulation in macrophages and binds to the IL-6 3′-UTR in macrophages. In RAW 264 cells, knockdown of Arid5a by siRNA led to the decrease of LPS-induced IL-6 but not TNF-α production. We showed that overexpression of Arid5a critically stabilizes IL-6 mRNA through AU-rich elements of the 3′-UTR region. Conclusion Thus, Arid5a is an IL-6 mRNA stability protein which mediates the inhibitory effects of CPZ on LPS-mediated IL-6 production. CPZ, or novel derivatives of this molecule, may represent a new therapy for IL6-dependent diseases (such as arthritis), through its inhibitory function on IL-6 mRNA stability.

Inhibitory Effect of Chlorpromazine on RANKL-Induced Osteoclastogenesis in Mouse Bone Marrow Cells

Chlorpromazine (CPZ), the first widely used phenothiazine tranquilizer, is shown to inhibit the action of intracellular calmodulin (CaM) and bone resorption in vivo and in vitro. In this study, CPZ (0.63 - 10 µM) dose-dependently inhibited the formation of tartrate-resistant acid phosphatase (TRAP) staining-positive osteoclast-like cells in mouse bone marrow cells (BMCs) treated with 1α,25(OH)(2)D(3) (10 nM) or soluble receptor activator of nuclear factor-κB ligand (s-RANKL) (20 ng/ml). Expressions of mRNA for the nuclear factor of activated T-cells c1 (NFATc1), a key regulator of osteoclast differentiation; dendritic cell-specific transmembrane protein (DC-STAMP), an essential protein for cell-cell fusion; and characteristic markers of osteoclasts such as TRAP, cathepsin K, carbonic anhydrase II, and calcitonin receptor in BMCs were up-regulated by s-RANKL and decreased by the addition of CPZ (5 µM) or the selective CaM antagonist W7, but not the inactive analog W5. The general CaM kinase (CaMK) inhibitor KN-93 and CaM-dependent phosphatase calcineurin inhibitor FK-506 also inhibited s-RANKL-induced osteoclastogenesis. Phenothiazines such as CPZ, trifluoperazine (TFPZ), and promethazine (PMZ) inhibited s-RANKL-induced osteoclast-like cell formation in mouse BMCs. Osteoclastogenesis inhibitory effects decreased in the order of TFPZ, CPZ, PMZ, depending on their anti-CaM potency. These findings suggest that CPZ inhibits RANKL-induced osteoclastogenesis by its anti-CaM action.

Chlorpromazine, clozapine and olanzapine inhibit anionic amino acid transport in cultured human fibroblasts

We report here that chlorpromazine, a first generation antipsychotic drug, inhibits anionic amino acid transport mediated by system X(-) (AG) (EAAT transporters) in cultured human fibroblasts. With 30 microM chlorpromazine, transport inhibition is detectable after 3 h of treatment, maximal after 48 h (>60%), and referable to a decrease in V(max). Chlorpromazine effect is not dependent upon changes of membrane potential and is selective for system X(-) (AG) since transport systems A and y(+) are not affected. Among antipsychotic drugs, the inhibitory effect of chlorpromazine is shared by two dibenzodiazepines, clozapine and olanzapine, while other compounds, such as risperidon, zuclopentixol, sertindol and haloperidol, are not effective. Transport inhibition by clozapine and olanzapine, but not by chlorpromazine, is reversible, suggesting that the mechanisms involved are distinct. These results indicate that a subset of antipsychotic drugs inhibits EAAT transporters in non-nervous tissues and prompt further investigation on possible alterations of glutamate transport in peripheral tissues of schizophrenic patients.

Intracellular trafficking of a palmitoylated membrane-associated protein component of enveloped vaccinia virus.

The F13L protein of vaccinia virus, an essential and abundant palmitoylated peripheral membrane component of intra- and extracellular enveloped virions, associates with Golgi, endosomal, and plasma membranes in the presence or absence of other viral proteins. In the present study, the trafficking of a fully functional F13L-green fluorescent protein (GFP) chimera in transfected and productively infected cells was analyzed using specific markers and inhibitors. We found that Sar1(H79G), a trans-dominant-negative protein inhibitor of cargo transport from the endoplasmic reticulum, had no apparent effect on the intracellular distribution of F13L-GFP, suggesting that the initial membrane localization occurs at a downstream compartment of the secretory pathway. Recycling of F13L-GFP from the plasma membrane was demonstrated by partial colocalization with FM4-64, a fluorescent membrane marker of endocytosis. Punctate F13L-GFP fluorescence overlapped with clathrin and Texas red-conjugated transferrin, suggesting that endocytosis occurred via clathrin-coated pits. The inhibitory effects of chlorpromazine and trans-dominant-negative forms of dynamin and Eps15 protein on the recycling of F13L-GFP provided further evidence for clathrin-mediated endocytosis. In addition, the F13L protein was specifically coimmunoprecipitated with alpha-adaptin, a component of the AP-2 complex that interacts with Eps15. Nocodazole and wortmannin perturbed the intracellular trafficking of F13L-GFP, consistent with its entry into late and early endosomes through the secretory and endocytic pathways, respectively. The recycling pathway described here provides a mechanism for the reutilization of the F13L protein following its deposition in the plasma membrane during the exocytosis of enveloped virions.

Inhibitory Effect of Chlorpromazine on Nematode Eggs and Larvae

Chlorpromazine inhibited the hatching of eggs of the parasitic nematode Haemonchus contortus and the free-living nematode Caenorhabditis elegans. In both species, hatching occurred at a concentration of 100 microg/ml but was almost totally blocked at 400 microg/ml. In the case of C. elegans, the effect was shown to be reversible by removal of chlorpromazine after exposure of the eggs to the drug for 1 hr. Caenorhabditis elegans larvae that hatched in a chlorpromazine concentration of 100 microg/ml were killed, but those that hatched in a concentration of 6.25 microg/ml were not. Taken together with data published by others, these observations indicate that the first-stage larva of C. elegans is less sensitive to chlorpromazine than is the adult worm.

Inhibitory effect on LPS-induced tumor necrosis factor in calves treated with chlorpromazine or pentoxifylline.

The inhibitory effect of chlorpromazine (CPZ), pentoxifylline (PTX) and dexamethasone (DEX) was investigated in a model of endotoxin shock in Holstein calves following an intravenous administration of Esherichia coli endotoxin (LPS). Initial correlations with its effects on the levels of tumor necrosis factor (TNF), a pivotal mediator of endotoxin shock, and clinical signs were obtained. The pretreatment of CPZ or DEX significantly decreased the serum levels of TNF, and reduced endotoxic shock. But the pretreatment of PTX hardly reduced the increase of serum TNF levels and endotoxin shock. The levels of serum endotoxin were not significantly different a minute of postinjection of LPS in calves. The results of this study indicate that pretreatment of CPZ or DEX inhibit various biological effects on endotoxin in calves.

Direct inhibitory effect of chlorpromazine on smooth muscle of the porcine pulmonary artery.

Chlorpromazine has been widely used by anesthesiologists to take advantage of its anesthesia-potentiating and vasorelaxing actions. However, the mechanisms of vasorelaxation induced by chlorpromazine are still not fully understood. Using front-surface fluorometry of fura-2 and porcine pulmonary arterial strips, we investigated the effects of chlorpromazine on the intracellular Ca2+ concentration ([Ca2+]i) and force of vascular smooth muscle. The affinities of chlorpromazine and other neuroleptics to vascular alpha(1)-adrenergic receptors were then determined by a radio-ligand binding study. Chlorpromazine (as much as 1 microM) inhibited both the elevation of [Ca2+]i and force in pulmonary arterial smooth muscle induced by 80 mM K+-depolarization and 1 microM norepinephrine in a concentration-dependent manner. The extent of inhibition by chlorpromazine in norepinephrine-induced contraction was much greater than that in 80 mM K+-induced contraction. In contrast, as much as 1 microM chlorpromazine had no effect on the increases in [Ca2+]i or force induced by U46619, a thromboxane A2 analogue. Chlorpromazine also had no effect on the intracellular Ca2+ release induced by U46619. In a radio-ligand displacement study, chlorpromazine, haloperidol, phentolamine, trifluoperazine, and imipramine inhibited the specific binding of [3H]prazosin to the porcine aortic membranes, in this order of potency. Chlorpromazine induces vasorelaxation through an alpha-adrenergic blocking action as well as a calcium antagonistic action; the former action may, therefore, play a major role in chlorpromazine-induced vasorelaxation.

Inhibitory effect of chlorpromazine on rat reproduction: A test of administration for nine weeks before breeding

The effect of chlorpromazine (CPZ) administration prior to insemination on reproduction was studied using male and female Sprague-Dawley strain rats evaluated over three generations. CPZ in doses of 12.5, 25, 50, and 100 mg/kg was administered to both male and female rats orally every day for 9 weeks before mating with the following results: 1) The duration of the estrous cycle was prolonged in the F 0 females. 2) The incidence of insemination and pregnancy of the F 0 males and females as well as the number of surviving fetuses and newborns showed a tendency to decrease. 3) The body weight of the rats in F 0 and F 1 generations decreased depending on the dose of CPZ, but the body weight of the F 2 generation increased. 4) The wet weight of the major organs of the rats in F 0 and F 1 generations was affected by administration of CPZ at 100 mg/kg. The weights of the liver, kidney, adrenal, pituitary, testis, and prostate glands in males and the kidney, adrenal gland, and ovary in females were increased, whereas the weights of the pituitary and the uterus were decreased in females. These results suggest that premating administration of CPZ to the parent rats exerts influence on the reproduction of the F 0 and F 1 generations.

Inhibitory effect of chlorpromazine on rat reproduction: A two week administration test before mating.

The effect of chlorpromazine (CPZ) administration before mating on reproduction was studied using male and female Sprague Dawley strain rats, and was evaluated over three generations. CPZ in dose of 12.5, 25, 50 and 100 mg/kg was orally administered to both male and female rats (F0 generation) every day for 2 weeks before mating with the following results: 1) The incidence of insemination and pregnancy of the F0 generation rats decreased but did not decrease in the F1 generation. While no influence of CPZ on the number of myometrial glands, on the length of pregnancy or on delivery was noted in either the F0 or F1 females, the number of surviving fetuses and newborns decreased in a dose-dependent fashion. 2) The body weight of rats in the F0 and F1 generations decreased depending on the dosage of CPZ, but the body weight of the F2 generation increased. 3) The wet weight of the major organs of the male and female rats in the F0 generation was affected by CPZ when administered at 100 mg/kg. The weight of the adrenal, pituitary and prostate glands in males, the adrenal gland and ovary in females increased, whereas the weight of the pituitary and uterus in females decreased. These results suggest that administering CPZ to the F0 rats before mating exerts an influence on the reproduction in both the F0 and F1 generations.

Suppression of Release of Microfilariae In vitro from Setaria cervi (Nematoda: Filariodeae) by Chlorpromazine

Chlorpromazine (CPZ) caused suppression in release of microfilariae in vitro from Setaria cervi at 10(-5) M concentration. The inhibitory effect of CPZ was further stimulated by Ca2+ (2 mM), whereas addition of EGTA (2 mM) resulted in partial reversal. Addition of dopamine (1 mM) along with CPZ (10(-5) M) caused similar inhibition as was observed in the presence of CPZ (10(-5) M) alone. CPZ did not effect in vitro oxygen uptake by worm homogenates up to 0.5 mM concentration. The results indicate the Ca2+/calmodulin-dependent anthelmintic action of CPZ on S. cervi.

Chlorpromazine and carnitine-dependency of rat liver peroxisomal beta-oxidation of long-chain fatty acids.

The enzyme targets for chlorpromazine inhibition of rat liver peroxisomal and mitochondrial oxidations of fatty acids were studied. Effects of chlorpromazine on total fatty acyl-CoA synthetase activity, on both the first and the third steps of peroxisomal beta-oxidation, on the entry of fatty acyl-CoA esters into the peroxisome and on catalase activity, which allows breakdown of the H2O2 generated during the acyl-CoA oxidase step, were analysed. On all these metabolic processes, chlorpromazine was found to have no inhibitory action. Conversely, peroxisomal carnitine octanoyltransferase activity was depressed by 0.2-1 mM-chlorpromazine, which also inhibits mitochondrial carnitine palmitoyltransferase activity in all conditions in which these enzyme reactions are assayed. Different patterns of inhibition by the drug were, however, demonstrated for both these enzyme activities. Inhibitory effects of chlorpromazine on mitochondrial cytochrome c oxidase activity were also described. Inhibitions of both cytochrome c oxidase and carnitine palmitoyltransferase are proposed to explain the decreased mitochondrial fatty acid oxidation with 0.4-1.0 mM-chlorpromazine reported by Leighton, Persico & Necochea [(1984) Biochem. Biophys. Res. Commun. 120, 505-511], whereas depression by the drug of carnitine octanoyltransferase activity is presented as the factor responsible for the decreased peroxisomal beta-oxidizing activity described by the above workers.

Brain stem involvement in the effects of chlorpromazine on the monosynaptic reflex of the rat lumbar spinal cord.

The brain stem areas involved in the inhibitory effect of chlorpromazine (CPZ) on the monosynaptic reflex (MSR) in the lumbar spinal cord of rats were investigated following brain stem transection and focal thermo-lesioning. Transection of the medulla oblongata markedly reduced the effect of CPZ, while transection in the mid-brain or more anterior level did not alter the effect of CPZ. With regard to focal lesions at various sites of the brain stem, lesioning of the medial portion of the medulla oblongata most effectively attenuated the MSR inhibition by CPZ and also attenuated the MSR inhibition induced by phenoxybenzamine. Bilateral lesioning of the locus coeruleus did not attenuate the MSR inhibition by CPZ. These results suggest that the pathway involved in the inhibitory effect of CPZ on the MSR originates in the pons and passes through the medial portion of the medulla oblongata, and that the coerulo-spinal pathway is not the major pathway involved in the effect of CPZ.

Inhibitory effect of phenothiazine derivatives on bone in vivo and osteoblastic cells in vitro.

We tested the inhibitory effects of phenothiazine derivatives on bone in vivo and osteoblastic cells in vitro. Chlorpromazine (CPZ) and trifluoperazine (TFPZ) dose-dependently decreased alkaline phosphatase activity in calvariae of rats: half-maximal inhibitory effects of CPZ and TFPZ were at 2.0 and 4.0 mg/kg, respectively. These effects were more specific for calvaria and ileum than for liver and duodenum. CPZ inhibited the proliferation of osteoblastic clone MC3T3-E1 cells to a greater extent than that of liver epithelial clone RLC-18(4) cells in vitro. CPZ, TFPZ and perphenazine (PNZ) also affected rather specifically alkaline phosphatase activity and collagen synthesis and were not cytotoxic. These in vivo and in vitro findings suggest inhibitory effects on osteoblastic cell function(s). However, promethazine (PMZ) had little effect in vivo and in vitro. In addition, increases in serum calcium and phosphate induced by CPZ indicate its possible involvement in bone resorption.

Inhibitory effect of chlorpromazine on bone formation in vivo and in vitro

Inhibitory effect of chlorpromazine on bone formation in vivo and in vitro

Inhibitory effects of chlorpromazine on Candida species.

Chlorpromazine was tested for antifungal activity by using Candida albicans and standard assays. The MIC of chlorpromazine was 35 micrograms/ml; the minimal fungicidal concentration was also 35 micrograms/ml. The minimal effective concentration was 2.2 to 3.5 micrograms/ml (using assays based on quantitative cultures and growth). There was a slight positive interaction between chlorpromazine and amphotericin B but no interaction between chlorpromazine and rifampin. Chlorpromazine also inhibited C. krusei, C. parapsilosis, C. tropicalis, and Torulopsis glabrata. We conclude that phenothiazines have direct anti-Candida activity and that these drugs appear to have a broad antimicrobial spectrum.

Effects of morphine and neuroleptics on wet-dog shaking behavior elicited by hippocampal stimulation in rats.

The relationship between wet-dog shaking (WDS) and afterdischarge (AD) elicited by dorsal hippocampal stimulation was investigated. The number of the WDS during a 150-s observation period was 9.6 +/- 2.0 (mean +/- SEM) and no WDS was seen during the non-seizure period. The effects of morphine and neuroleptics on WDS and AD were also investigated. Morphine significantly inhibited the number of WDS elicited by hippocampal stimulation. Naloxone significantly antagonized the inhibitory effect of morphine. Haloperidol and chlorpromazine significantly and dose-dependently inhibited the number of WDS at very small doses. The inhibitory effect of chlorpromazine on WDS was not antagonized by pretreatment with naloxone. The present results suggest that central dopaminergic mechanisms may be important in WDS elicited by hippocampal stimulation. The effect of morphine on WDS is probably mediated via an opioid receptor having a modulating effect on central dopaminergic mechanisms.

Membrane stabilizers inhibit potassium efflux from Staphylococcus aureus strain No. U2275

The effect of different categories of membrane stabilizers on K + loss and growth has been characterized in a culture of Staphylococcus aureus. Chlorpromazine, thiopental and tetracaine at low concentrations produced a marked inhibition of K + loss and an equivalent increase in the K + contents of S. aureus. Whereas the inhibitory effect of chlorpromazine on K + loss was observed at lower than bacteriostatic concentrations of the drug, thiopental had no effect on growth in the concentration range where K + loss was maximally inhibited. It is concluded that the bacteriostatic action of chlorpromazine is probably not related to its membrane stabilizing effect only.