Orthostatic hypotensive effect of antipsychotic drugs in Wistar rats by in vivo and in vitro studies of α1-adrenoceptor function

Nourian, Zahra; Mow, Tomas; Muftic, D.; Burek, S.; Pedersen, Mette Lund; Matz, Jørgen; Mulvany, Michael J.

doi:10.1007/s00213-007-1064-9

Cited by 28 publications

(18 citation statements)

References 44 publications

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“…Almost universally, antipsychotics cause orthostatic hypotension. 52 Interestingly, cell model showed much higher (B10-fold) antagonist affinity of sertindole and risperidone than haloperidol for recombinant human ADRA1A, which is consistent with the findings in rat model 53 and human post-mortem study. 54 The high ADRA1A affinity of sertindole and risperidone explains the relatively high incidence of dizziness in patients taking sertindole 55 and risperidone 56 compared with those taking haloperidol.…”

Section: Y-r Liu Et Alsupporting

confidence: 83%

ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics

et al. 2009

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Noradrenaline and adrenaline are neurotransmitters of the sympathetic nervous system that interact with various adrenergic receptor (ADR) subtypes, and this regulates the basal metabolic rate, thermogenesis and efficiency of energy utilization. We examined a possible role of the gene coding for ADRA1A receptor in weight gain in schizophrenia subjects exposed to antipsychotics. A total of 401 schizophrenia in-patients treated with antipsychotics for 42 years were recruited and a final 394 DNA samples were genotyped. Their body mass indexes (BMIs) were recorded for 12 months and parameterized to be correlated in regression. Among the 58 single-nucleotide polymorphisms (SNPs) genotyped, 44 valid SNPs, which had minor allele frequency X0.03, were analyzed in statistics. Linear regression model with age, gender, diabetes, use of typical antipsychotics and use of atypical antipsychotics as covariates, with or without gender interaction, showed evidence of associations between the ADRA1A gene and BMI. Most of the SNPs associated with BMI are located in the promoter and intron regions, and being female appeared to enhance the gene effect. Our study suggests that the ADRA1A gene is involved in weight gain among schizophrenia patients treated with antipsychotics. Further molecular dissection of the ADRA1A gene warrants better understanding on weight gain mechanisms in schizophrenia.

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Section: Y-r Liu Et Alsupporting

confidence: 83%

ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics

et al. 2009

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“…Falls sometimes lead to hip fracture, transient ischemic attacks, myocardial infarction in rare occasions, and, ultimately, to death in the most severe cases 107. Orthostatic (or postural) hypotension is thought to be mediated by α-1 receptor blockade and should be expected from antipsychotics with a high affinity to this receptor, such as ILO, ZIP, RIS, QUE, ASE, HAL, CPZ, and PER,108 according to animal models. In human beings, CLO, among SGAs, most increases the risk of hypotension, especially at the beginning of treatment, which is the reason behind low initial doses 94…”

Section: Methodsmentioning

confidence: 99%

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Solmi

Murru

Pacchiarotti

et al. 2017

TCRM

324

244

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Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis.

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“…A subcutaneous dose of 0.25 m/kg was shown to produce marked effects on posture-related blood pressure changes (Smirk & Alstad, 1951). Prazosin is a sympatholytic, which acts as an alpha-1 adrenergic receptor antagonist and has been shown to cause OH in humans as well as animal models including cats, dogs and rodents (Baum, Vander Vliet, Glennon, & Novak, 1981;Karasawa, Kubo, Yamada, Shuto, & Nakamizo, 1982;Nourian et al, 2008). In this study, prazosin caused a dose-dependent increases in OH incidence (5/8, 6/8 and 8/8 at 0.005, 0.015 and 0.05 mg/kg, respectively (Table 1)).…”

Section: Discussionmentioning

confidence: 52%

A non-human primate model for investigating drug-induced risk of orthostatic hypotension and sympathetic dysfunction: Preclinical correlate to a clinical test

Bhatt

Foote

Smith

et al. 2015

Journal of Pharmacological and Toxicological Methods

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Orthostatic hypotensive effect of antipsychotic drugs in Wistar rats by in vivo and in vitro studies of α1-adrenoceptor function

Abstract: We conclude that the orthostatic hypotensive effect in rats of the antipsychotic drugs investigated is mediated through alpha1A-ARs.

Cited by 28 publications

References 44 publications

ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics

ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

A non-human primate model for investigating drug-induced risk of orthostatic hypotension and sympathetic dysfunction: Preclinical correlate to a clinical test

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