Repurposing of Iloperidone: Antihypertensive and ocular hypotensive activity in animals

Joshi, Shrikant V; Patel, Ekta; Vyas, Bhavin; Lodha, Sandesh; Kalyankar, Gajanan G.

doi:10.1016/j.ejps.2019.105173

Cited by 4 publications

(4 citation statements)

References 35 publications

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“…In addition, iloperidone may become a drug of choice if the posttraumatic disorder is associated with psychosis, as α 1 receptor antagonism is the putative mechanism behind the efficacy of prazosin in improving sleep efficiency [85]. Similarly, iloperidone can be beneficial in managing comorbid hypertension in psychotic or posttraumatic patients [86]. Thus, overall, iloperidone may have one of the lowest risks of causing akathisia [84].…”

Section: Second-generation Antipsychotic Medications (Sgapms)mentioning

confidence: 99%

Seventy Years of Antipsychotic Development: A Critical Review

Shad

2023

Biomedicines

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Since the mid-1950s discovery of the first effective antipsychotic medications (APM), we have only been able to improve the tolerability but not the overall efficacy of currently available APMs, as reflected by effectiveness trials in Europe and the United States. This inability to develop more effective APMs is attributable to multiple factors, including failure to create and use assessment tools to assess core symptom domains in schizophrenia, move beyond the dopaminergic hypothesis and to develop “me too” drugs, imposing ill-defined research domain criteria, and lacking federal funding for clinical trials. The classification of APMs is also confusing, including second-generation, partial agonists, and multimodal APMs in the same class of APMs, despite significant differences in their mechanisms of action. Other factors stagnating drug development include inadequate sample sizes to address heterogeneity, lack of statistical measures correlating with clinical significance, using the atheoretical basis of psychiatric diagnoses, failure to control placebo response, and high cost of newer and perhaps more tolerable APMs. Furthermore, there has been a failure to develop early predictors of antipsychotic response and various tools to optimize an APM response. Finally, some mental health providers are also responsible for the suboptimal use of APMs, by using excessive maintenance doses, often with irrational polypharmacy, further compromising effectiveness and medication adherence. However, some bright spots in antipsychotic development include improved tolerability of APMs and long-acting injectables to address the high prevalence of medication nonadherence. This review critically reviews 70 years of antipsychotic development, the reasons behind the failure to develop more effective APMs, and suggestions for future direction.

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Section: Second-generation Antipsychotic Medications (Sgapms)mentioning

confidence: 99%

Seventy Years of Antipsychotic Development: A Critical Review

Shad

2023

Biomedicines

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“…Iloperidone can inhibit serotonergic 5HT2A receptor (J-13) and adrenergic alpha 1A receptor [ 143 , 144 ] and is responsible for hypotension [ 145 ]. In dose 0.03 mg/Kg i.p., Iloperidone present reduced blood pressure within the 10 min of administration for animals [ 146 ]. Only drug-induced angle-closure glaucoma is of direct relevance for AAPs administration.…”

Section: Lithium and Aaps In Glaucomamentioning

confidence: 99%

Lithium and Atypical Antipsychotics: The Possible WNT/β Pathway Target in Glaucoma

Vallée

Lecarpentier³

2021

Biomedicines

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Glaucoma is a progressive neurodegenerative disease that represents the major cause of irreversible blindness. Recent findings have shown which oxidative stress, inflammation, and glutamatergic pathway have main roles in the causes of glaucoma. Lithium is the major commonly used drug for the therapy of chronic mental illness. Lithium therapeutic mechanisms remain complex, including several pathways and gene expression, such as neurotransmitter and receptors, circadian modulation, ion transport, and signal transduction processes. Recent studies have shown that the benefits of lithium extend beyond just the therapy of mood. Neuroprotection against excitotoxicity or brain damages are other actions of lithium. Moreover, recent findings have investigated the role of lithium in glaucoma. The combination of lithium and atypical antipsychotics (AAPs) has been the main common choice for the treatment of bipolar disorder. Due to the possible side effects gradually introduced in therapy. Currently, no studies have focused on the possible actions of AAPs in glaucoma. Recent studies have shown a down regulation of the WNT/β-catenin pathway in glaucoma, associated with the overactivation of the GSK-3β signaling. The WNT/β-catenin pathway is mainly associated with oxidative stress, inflammation and glutamatergic pathway. Lithium is correlated with upregulation the WNT/β-catenin pathway and downregulation of the GSK-3β activity. Thus, this review focuses on the possible actions of lithium and AAPs, as possible therapeutic strategies, on glaucoma and some of the presumed mechanisms by which these drugs provide their possible benefit properties through the WNT/β-catenin pathway.

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“…Risperidone, clozapine, iloperidone and quetiapine may lead to hypotension via this mechanism [34]. Animal studies showed instilled APP into the eye determined a significant reduction of IOP observed after 1 h. Also, reduction of blood pressure occurred within 10 min after administration [84].…”

Section: Antipsychoticsmentioning

confidence: 99%

Psychopharmacological Treatment, Intraocular Pressure and the Risk of Glaucoma: A Review of Literature

Ciobanu

Dionisie

Neagu

et al. 2021

JCM

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Through the years, the available psychopharmacological treatments have expanded with numerous new drugs. Besides weight gain, gastro-intestinal problems or Parkinson-like symptoms, ocular adverse effects of psychiatric drugs have been reported. These adverse effects are not common, but can be dangerous for the patient. This review summarises the current knowledge on the risk of raised intraocular pressure and glaucoma entailed by psychopharmacological treatment. Also, it provides updated data for clinicians involved in the treatment of patients with glaucoma or glaucoma risk factors. For this purpose, we performed an extensive literature search in the PubMed database using specific terms. Selective serotonin and noradrenaline reuptake inhibitors are the best evidenced as having no association with glaucoma. Antipsychotics, and especially first generation, seem to have no correlation with an increased intraocular pressure and therefore possibly with a risk of glaucoma, although a special attention should be paid when using ziprasidone. Tricyclic antidepressants, benzodiazepines and topiramate should be avoided in patients diagnosed with glaucoma or at risk. Clinicians should be aware of the possible psychotropic drug induced glaucoma and monitor at risk patients closely in order to prevent this condition. Irrespective of the psychopharmacological regimen taken into consideration, the glaucoma patient should be under the strict supervision of the ophthalmologist.

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Repurposing of Iloperidone: Antihypertensive and ocular hypotensive activity in animals

Cited by 4 publications

References 35 publications

Seventy Years of Antipsychotic Development: A Critical Review

Seventy Years of Antipsychotic Development: A Critical Review

Lithium and Atypical Antipsychotics: The Possible WNT/β Pathway Target in Glaucoma

Psychopharmacological Treatment, Intraocular Pressure and the Risk of Glaucoma: A Review of Literature

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