Elevation of systolic blood pressure in an animal model of olanzapine induced weight gain

Patil, B. M.; Kulkarni, Nagaraj M.; Unger, Banappa S.

doi:10.1016/j.ejphar.2006.09.009

Cited by 28 publications

(11 citation statements)

References 20 publications

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“…Two separate techniques were used to measure metabolic dysregulation, including both the glucose tolerance test and the hyperinsulinemic-euglycemic clamp. Consistent with previous preclinical studies, olanzapine caused dose-dependent glucose intolerance in the IGTT and insulin resistance in the clamp [26], [27], [40]–[47]. By contrast, the novel SGA drug asenapine was largely devoid of metabolic effects at the doses tested, causing only a slight reduction in insulin levels and HOMA-IR values with the lowest dose.…”

Section: Discussionsupporting

confidence: 86%

Metabolic Side-Effects of the Novel Second-Generation Antipsychotic Drugs Asenapine and Iloperidone: A Comparison with Olanzapine

et al. 2013

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BackgroundThe second generation antipsychotic (SGA) drugs are widely used in psychiatry due to their clinical efficacy and low incidence of neurological side-effects. However, many drugs in this class cause deleterious metabolic side-effects. Animal models accurately predict metabolic side-effects for SGAs with known clinical metabolic liability. We therefore used preclinical models to evaluate the metabolic side-effects of glucose intolerance and insulin resistance with the novel SGAs asenapine and iloperidone for the first time. Olanzapine was used as a comparator.MethodsAdults female rats were treated with asenapine (0.01, 0.05, 0.1, 0.5, 1.0 mg/kg), iloperidone (0.03, 0.5, 1.0, 5.0, 10.0 mg/kg) or olanzapine (0.1, 0.5, 1.5, 5.0, 10.0 mg/kg) and subjected to the glucose tolerance test (GTT). Separate groups of rats were treated with asenapine (0.1 and 1.0 mg/kg), iloperidone (1.0 and 10 mg/kg) or olanzapine (1.5 and 15 mg/kg) and tested for insulin resistance with the hyperinsulinemic-euglycemic clamp (HIEC).ResultsAsenapine showed no metabolic effects at any dose in either test. Iloperidone caused large and significant glucose intolerance with the three highest doses in the GTT, and insulin resistance with both doses in the HIEC. Olanzapine caused significant glucose intolerance with the three highest doses in the GTT, and insulin resistance with the higher dose in the HIEC.ConclusionsIn preclinical models, asenapine shows negligible metabolic liability. By contrast, iloperidone exhibits substantial metabolic liability, comparable to olanzapine. These results emphasize the need for appropriate metabolic testing in patients treated with novel SGAs where current clinical data do not exist.

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Section: Discussionsupporting

confidence: 86%

Metabolic Side-Effects of the Novel Second-Generation Antipsychotic Drugs Asenapine and Iloperidone: A Comparison with Olanzapine

et al. 2013

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“…The findings with the IGTT reconfirm the powerful effects of the SGA olanzapine in animal models of glucose dysregulation (Albaugh et al, 2006;Boyda et al, 2010b;Chintoh et al, 2008b;Cooper et al, 2005;Houseknecht et al, 2007;Martins et al, 2011;Patil et al, 2006;Smith et al, 2011;Victoriano et al, 2009), which parallel the effects seen in humans (Boyda et al, 2010a). Rats that were treated daily with 10 mg/kg of olanzapine (Mon-Fri) exhibited pronounced glucose intolerance in the IGTT, which remained stable in magnitude when tested weekly over a 9 wk period.…”

Section: Discussionsupporting

confidence: 56%

Routine exercise ameliorates the metabolic side-effects of treatment with the atypical antipsychotic drug olanzapine in rats

Boyda

Ramos-Miguel

Procyshyn

et al. 2013

Int. J. Neuropsychopharm.

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Second generation antipsychotic (SGA) drugs are effective treatments for psychosis. Common side-effects of SGAs include metabolic dysregulation and risk of cardiometabolic disorders. Metabolic side-effects, including glucose intolerance, can be accurately modelled in rodents. The benefits of interventions used for treating metabolic side-effects of SGAs are mostly unknown. In a 9 wk longitudinal study, female rats were given daily olanzapine (10 mg/kg s.c.) or vehicle. Animals were either sedentary or allowed 1 or 3 h daily access to a running wheel, with total wheel revolutions electronically quantified to reflect exercise intensity. Glucose tolerance tests were performed once weekly to measure glycemic control. Drug levels were measured at week 4. At week 9, abdominal fat and skeletal muscle levels of Glucose Transporter 4 (GLUT4) were measured. Exercise intensity progressively increased over time in all groups given access to running wheels; however, rats treated with olanzapine consistently exercised less than those given the vehicle. Olanzapine caused acute and persistent glucose intolerance throughout the study, which was markedly, though incompletely, ameliorated by exercise. Exercise did not affect glycemic regulation in vehicle-treated rats. Olanzapine-treated rats showed greater central adiposity. Levels of GLUT4 in skeletal muscle were higher in both groups of exercising than in sedentary rats, and GLUT4 values were negatively correlated with glucose intolerance. Routine exercise reduced olanzapine-induced glucose intolerance and increased skeletal muscle levels of GLUT 4, the insulin-responsive transporter that mediates glucose uptake into cells. The current animal model is suitable for evaluating physiological pathways involved with glucose intolerance.

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“…The limitation of our study includes that we might have evaluated the blood pressure because blood pressure is the one of the important component for the diagnosis of metabolic syndrome [35]. Patil et al (2006) reported that chronic treatment with olanzapine (1 and 2 mg/kg) elevates systolic blood pressure in normal rats [10]. Derosa et al (2004) reported that telmisartan reduces blood pressure in patients with type-2 diabetes mellitus and mild hypertension [12].…”

Section: Discussionmentioning

confidence: 99%

“…In the clinical setting, the identifying characteristics of antipsychotic drug-induced metabolic disorders are weight gain, hypertension, hyperlipidemia, hyperglycemia, glucose intolerance and insulin resistance [8]. Olanzapine and clozapine are more prone to induce these metabolic side-effects than other atypical antipsychotic drugs [10]. Many reports have found a higher prevalence of metabolic syndrome in patients with schizophrenia compared to the general population [11].…”

Section: Introductionmentioning

confidence: 99%

Effect of Telmisartan on Olanzapine Induced Metabolic Syndrome in Ovariectomized Female Sprague-Dawley Rats

Pavani

2012

J Endocrinol Metab

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Background: Menopause increases the prevalance of metabolic syndrome in women. Olanzapine is an atypical antipsychotic drug which is used in the treatment of psychiatric disorders, include schizophrenia and bipolar disorder. But it is associated with serious metabolic side-effects, include weight gain, hypertension, hyperlipidemia, hyperglycemia, glucose intolerance and insulin resistance which results in metabolic syndrome. The prevalence of metabolic syndrome is more in patients with schizophrenia compared to the general population. Telmisartan an antihypertensive agent, is an angiotensin II type-I receptor blocker (ARB) also activates peroxisome proliferator-activated receptor gamma (PPARγ) and provide beneficial effects for glucose and lipid metabolism. Thus the objective of the present study was to evaluate the effect of telmisartan and additional influence of menopause status on olanzapine induced metabolic syndrome in female Sprague-Dawley rats. Methods: After four weeks of ovariectomy, olanzapine (5 mg/kg) was administered by oral route for 28 days to induce metabolic syndrome in female Sprague-Dawley rats. Thirty female Sparague-Dawley rats were randomly divided into five groups as normal control; ovariectomy control (OVX); ovariectomy + olanzapine control (OVX+OLZ); OVX + Telmisartan (5 mg/kg); OVX + OLZ + Telmisartan (5 mg/kg). After 28 days of treatment, the blood samples were collected and analyzed for blood glucose, plasma insulin, lipid profiles, SGOT, SGPT and body weights of all groups were recorded. Results: OVX control and OVX + OLZ control groups showed significant (P < 0.01) increase in body weight, blood glucose, plasma insulin, total cholesterol, triglycerides, LDL-C, VLDL-C, SGOT, SGPT and significant (P < 0.01) decrease in HDL-C when compared to normal control. While OVX group and OVX + OLZ group treated with telmisartan showed significant decrease in body weight gain (P < 0.05), blood glucose (P < 0.01), plasma insulin (P < 0.01), total cholesterol (P < 0.01), triglycerides (P < 0.05, P < 0.01), LDL-C (P < 0.01), VLDL-C (P < 0.05, P < 0.01), SGOT (P < 0.05, P < 0.01), SGPT (P < 0.01) and significant increase in HDL-C (P < 0.01) when compared to OVX control and OVX + OLZ control group. The results of histopathological studies provide strong support to our results. Conclusions: Telmisartan attenuate the development of metabolic syndrome induced by olanzapine in ovariectomized female Sprague-Dawley rats.

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Elevation of systolic blood pressure in an animal model of olanzapine induced weight gain

Cited by 28 publications

References 20 publications

Metabolic Side-Effects of the Novel Second-Generation Antipsychotic Drugs Asenapine and Iloperidone: A Comparison with Olanzapine

Metabolic Side-Effects of the Novel Second-Generation Antipsychotic Drugs Asenapine and Iloperidone: A Comparison with Olanzapine

Routine exercise ameliorates the metabolic side-effects of treatment with the atypical antipsychotic drug olanzapine in rats

Effect of Telmisartan on Olanzapine Induced Metabolic Syndrome in Ovariectomized Female Sprague-Dawley Rats

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