The blood concentration and organ distribution of haloperidol at therapeutic and toxic doses in severe fatty liver disease

Ikemura, Mayumi; Nakagawa, Yasuhisa; Shinone, Kotaro; Inoue, Hiromasa; Nata, Masayuki

doi:10.1016/j.legalmed.2012.01.012

Cited by 5 publications

(3 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, the therapeutic plasma levels of olanzapine and clozapine are approximately 0.3 to 3 μM respectively [62], whereas the concentrations used in vitro normally range between 1 and 100 μM. That being said, it has been reported that the concentration of SGAs in rodent tissues could be 20–100-fold higher than those in plasma [63,64].…”

Section: New Insights Into the Molecular Mechanisms By Which Sgas mentioning

confidence: 99%

Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain

Grajales

Ferreira

Valverde

2019

Cells

122

View full text Add to dashboard Cite

Second-generation antipsychotics (SGAs) are the cornerstone of treatment for schizophrenia because of their high clinical efficacy. However, SGA treatment is associated with severe metabolic alterations and body weight gain, which can increase the risk of type 2 diabetes and cardiovascular disease, and greatly accelerate mortality. Several underlying mechanisms have been proposed for antipsychotic-induced weight gain (AIWG), but some studies suggest that metabolic changes in insulin-sensitive tissues can be triggered before the onset of AIWG. In this review, we give an outlook on current research about the metabolic disturbances provoked by SGAs, with a particular focus on whole-body glucose homeostasis disturbances induced independently of AIWG, lipid dysregulation or adipose tissue disturbances. Specifically, we discuss the mechanistic insights gleamed from cellular and preclinical animal studies that have reported on the impact of SGAs on insulin signaling, endogenous glucose production, glucose uptake and insulin secretion in the liver, skeletal muscle and the endocrine pancreas. Finally, we discuss some of the genetic and epigenetic changes that might explain the different susceptibilities of SGA-treated patients to the metabolic side-effects of antipsychotics.

show abstract

Section: New Insights Into the Molecular Mechanisms By Which Sgas mentioning

confidence: 99%

Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain

Grajales

Ferreira

Valverde

2019

Cells

122

View full text Add to dashboard Cite

show abstract

“…It is prescribed in several diagnoses, such as psychosis, manic phases, hyperactivity, aggressiveness and acute delirium, and in certain cases, it is employed in long-term treatment. However, the use of typical neuroleptic drugs is limited by their side-effects and toxicity (2–6). Despite significant advantages provided by these remedies, patients using these drugs have to cope with the residual symptomatology which interferes significantly with their social and occupational life (7).…”

Section: Introductionmentioning

confidence: 99%

Determination of oxidative stress and activities of antioxidant enzymes in guinea pigs treated with haloperidol

Gumulec

Raudenská

Hlavna

et al. 2012

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Guinea pigs (Cavia porcellus) were treated with haloperidol (HP), and free radical (FR) and ferric reducing antioxidant power (FRAP) assays were used to determine oxidative stress levels. Furthermore, the superoxide dismutase (SOD), glutathione reductase (GR) and glutathione-S-transferase (GST) activity levels were detected and glucose levels and the reduced and oxidized glutathione (GSH/GSSG) ratio were measured in HP-treated and untreated guinea pigs. The present study demonstrated that the administration of HP causes significant oxidative stress in guinea pigs (P=0.022). In animals treated with HP, the activity of GST was significantly increased compared with a placebo (P= 0.007). The elevation of SOD and GR activity levels and increase in the levels of glutathione (GSH) in HP-treated animals were not statistically significant. In the HP-untreated animals, a significant positive correlation was observed between oxidative stress detected by the FR method and GST (r=0.88, P=0.008) and SOD (r=0.86, P= 0.01) activity levels, respectively. A significant negative correlation between the levels of plasma glucose and oxidative stress detected by the FRAP method was observed (r=−0.78, P=0.04). Notably, no significant correlations were observed in the treated animals. In the HP-treated group, two subgroups of animals were identified according to their responses to oxidative stress. The group with higher levels of plasma HP had higher enzyme activity and reactive oxygen species production compared with the group with lower plasma levels of HP. The greatest difference in activity (U/μl) between the two groups of animals was for GR.

show abstract

“…In our experiments, the haloperidol plasma level was under the limit of our detection even after 30 min, but significant amounts of drug were found in the brain, liver and lung. Since around 0.1 μg g −1 concentration of haloperidol is considered to have therapeutic action in rats [27], the 0.16 μg g −1 concentration that was found after 1 h in the brain of our rats seems to be satisfactory to provide the required neuroleptic effect.…”

Section: Discussionmentioning

confidence: 57%

Detection of stress and the effects of central nervous system depressants by gastrointestinal smooth muscle electromyography in wakeful rats

et al. 2018

View full text Add to dashboard Cite

show abstract

The blood concentration and organ distribution of haloperidol at therapeutic and toxic doses in severe fatty liver disease

Cited by 5 publications

References 34 publications

Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain

Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain

Determination of oxidative stress and activities of antioxidant enzymes in guinea pigs treated with haloperidol

Detection of stress and the effects of central nervous system depressants by gastrointestinal smooth muscle electromyography in wakeful rats

Contact Info

Product

Resources

About