Multi-target therapeutics for neuropsychiatric and neurodegenerative disorders

Bawa, Priya; Pradeep, Priyamvada; Kumar, Pradeep; Choonara, Yahya E.; Modi, Girish; Pillay, Viness

doi:10.1016/j.drudis.2016.08.001

Cited by 41 publications

(32 citation statements)

References 273 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Inflammation might be related to both psychopathology and other disturbances in patients with schizophrenia, since insulin resistance and metabolic alterations are common in these patients 20,28,29. Schizophrenia is also correlated with poor physical health, including higher rates of obesity, diabetes, hypertension and cardiovascular disease 16,30…”

Section: Resultsmentioning

confidence: 99%

“…Iloperidone has been accepted on the market after 12 years of premarketing evaluation and was approved by the US Food and Drug Administration (FDA) in May 2009, becoming available for use in early 2010. Recently (2013), the European Medicines Agency (EMA) has accepted evaluation of this drug application 30,37,39…”

Section: Resultsmentioning

confidence: 99%

“…Currently, there is no formal pharmacoeconomic study on the cost-effectiveness of iloperidone for treating schizophrenia. An estimated monthly acquisition cost comparison among usual maintenance doses of atypical antipsychotics showed that the cost of iloperidone of $630 is $50 more than that of asenapine, $200 more than that of ziprasidone and $400 more than the cost of generic risperidone 30,40. Thus, when referring only to acquisition costs of iloperidone, the higher price can hamper its use in clinical practice.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Iloperidone in the treatment of schizophrenia: an evidence-based review of its place in therapy

Tonin¹,

Wiens²,

Fernández-Llimós³

et al. 2016

View full text Add to dashboard Cite

IntroductionSchizophrenia is a chronic and debilitating mental disorder that affects the patient’s and their family’s quality of life, as well as financial costs and health care settings. Despite the variety of available antipsychotics, optimal treatment outcomes are not always achieved. Novel drugs, such as iloperidone, can provide more effective, tolerable and safer strategies.AimTo review the evidence for the clinical impact of iloperidone on the treatment of patients with schizophrenia.Evidence reviewClinical trials, observational studies and meta-analyses reached a common consensus that iloperidone is as effective as haloperidol, risperidone and ziprasidone in reducing schizophrenia symptoms. Similar amounts of adverse events and discontinuations were observed with iloperidone compared to placebo and active treatments. Common adverse events are mild and include dizziness, hypotension, dry mouth and weight gain. Iloperidone can induce extension of QTc interval, and clinicians should be aware of its contraindications. In long-term trials, iloperidone also showed promising safety and tolerability profiles. The low propensity to cause akathisia, extrapyramidal symptoms (EPS), increased prolactin levels or changes to metabolic laboratory parameters support its use in practice. Results showed that iloperidone prevents relapse in stabilized patients, with a time to relapse superior to placebo and similar to haloperidol. Patients using a prior antipsychotic (eg, risperidone and aripiprazole) can easily switch to iloperidone with no serious impact on safety or efficacy. However, the acquisition costs of iloperidone may hamper its use. Further evidence comparing iloperidone with other antipsychotics, and pharmacoeconomic studies would be welcome.Place in therapyConsidering just the clinical profile of iloperidone, it represents a promising drug for treating schizophrenia, particularly in patients who are intolerant to previous antipsychotics, as well as being suitable as first-line therapy. Cost-effectiveness comparisons are needed to justify its use in clinical practice.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Iloperidone in the treatment of schizophrenia: an evidence-based review of its place in therapy

Tonin¹,

Wiens²,

Fernández-Llimós³

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The term "one-target-one-disease" has been growing during the discovery of new drugs in recent years, mainly due to the complexity of some diseases (Bawa et al, 2016). Among these drugs, another term is "cocktail therapy," which is based on the combination of several drugs in clinical practice, in which these various drugs can act on several targets and may have synergistic effects in treatment.…”

Section: Introductionmentioning

confidence: 99%

Drug discovery and computational strategies in the multitarget drugs era

Viana

Félix

Maia

et al. 2018

Braz. J. Pharm. Sci.

View full text Add to dashboard Cite

The pharmaceutical industry is increasingly joining chemoinformatics in the search for the development of new drugs to be used in the treatment of diseases. These computational studies have the advantage of being less expensive and optimize the study time, and thus the interest in this area is increasing. Among the techniques used is the development of multitarget directed ligands (MTDLs), which has become an ascending technique, mainly due to the improvement in the quality of treatment involving several drugs. Multitarget therapy is more effective than traditional drug therapy that emphasizes maximum selectivity for a single target. In this review a multitarget drug survey was carried out as a promising strategy in several important diseases: neglected diseases, neurodegenerative diseases, AIDS, and cancer. In addition, we discuss Computer-Aided Drug Design (CADD) techniques as a tool in the projection of multitarget compounds against these diseases.

show abstract

“…It has been widely demonstrated that the etiology of complex diseases is the result of a combination of multiple environmental and genetic factors [2] ; thus, limited clinical outcomes may arise from intervention with one target among the complicated network of the disease. The need to apply multi-target combination therapeutic strategy has been increasingly recognized [3] . On the other hand, with the advance of genomics technology, precision medicine in recent years has aimed to achieve personalized treatment based on each individual's genetic disposition, which circumscribes the differing response to treatment [4] .…”

Section: Introductionmentioning

confidence: 99%

Full genetic analysis for genome-wide association study of Fangji: a powerful approach for effectively dissecting the molecular architecture of personalized traditional Chinese medicine

2018

View full text Add to dashboard Cite

Elucidation of the systems biology foundation underlying the effect of Fangji, which are multi-herbal traditional Chinese medicine (TCM) formulas, is one of the major aims in the field. The numerous bioactive ingredients of a Fangji deal with the multiple targets of a complex disease, which is influenced by a number of genes and their interactions with the environment. Genome-wide association study (GWAS) is an unbiased approach for dissecting the genetic variants underlying complex diseases and individual response to a given treatment. GWAS has great potential for the study of systems biology from the point of view of genomics, but the capacity using current analysis models is largely handicapped, as evidenced by missing heritability. Recent development of a full genetic model, in which gene-gene interactions (dominance and epistasis) and gene-environment interactions are all considered, has addressed these problems. This approach has been demonstrated to substantially increase model power, remarkably improving the detection of association of GWAS and the construction of the molecular architecture. This analysis does not require a very large sample size, which is often difficult to meet for a GWAS of treatment response. Furthermore, this analysis can integrate other omic information and allow for variations of Fangji, which is very promising for Fangjiomic study and detection of the sophisticated molecular architecture of the function of Fangji, as well as for the delineation of the systems biology of personalized medicine in TCM in an unbiased and comprehensive manner.

show abstract

Multi-target therapeutics for neuropsychiatric and neurodegenerative disorders

Cited by 41 publications

References 273 publications

Iloperidone in the treatment of schizophrenia: an evidence-based review of its place in therapy

Iloperidone in the treatment of schizophrenia: an evidence-based review of its place in therapy

Drug discovery and computational strategies in the multitarget drugs era

Full genetic analysis for genome-wide association study of Fangji: a powerful approach for effectively dissecting the molecular architecture of personalized traditional Chinese medicine

Contact Info

Product

Resources

About