Drug Repurposing Is a New Opportunity for Developing Drugs against Neuropsychiatric Disorders.

Hyeong-Min Lee,Yuna Kim

doi:10.1155/2016/6378137

Abstract

Better the drugs you know than the drugs you do not know. Drug repurposing is a promising, fast, and cost effective method that can overcome traditional de novo drug discovery and development challenges of targeting neuropsychiatric and other disorders. Drug discovery and development targeting neuropsychiatric disorders are complicated because of the limitations in understanding pathophysiological phenomena. In addition, traditional de novo drug discovery and development are risky, expensive, and time-consuming processes. One alternative approach, drug repurposing, has emerged taking advantage of off-target effects of the existing drugs. In order to identify new opportunities for the existing drugs, it is essential for us to understand the mechanisms of action of drugs, both biologically and pharmacologically. By doing this, drug repurposing would be a more effective method to develop drugs against neuropsychiatric and other disorders. Here, we review the difficulties in drug discovery and development in neuropsychiatric disorders and the extent and perspectives of drug repurposing.

Highlights

The principle of “polypharmacology” has been understood since the advent of drug discovery
Drug promiscuity represents either good or bad effects mediated by compounds binding to both therapeutic and nontherapeutic targets, whereas polypharmacology represents beneficial effects mediated by compounds binding to multiple therapeutic targets
Despite the exponential growth of advanced technology and the resultant molecular database, we still do not fully understand the signaling pathways and molecular mechanisms behind many disease states, especially neuropsychiatric disorders. This lack of knowledge makes repurposing drugs difficult and that is a direct application of polypharmacology

Summary

Introduction

The principle of “polypharmacology” (i.e., one drug, multiple hits, or off-target effects) has been understood since the advent of drug discovery. Drug promiscuity represents either good or bad effects mediated by compounds binding to both therapeutic and nontherapeutic targets, whereas polypharmacology represents beneficial effects mediated by compounds binding to multiple therapeutic targets Various drug classes such as selective serotonin reuptake inhibitors [1, 2], antipsychotic [3], cholinesterase inhibitors [4], and thrombolytic agents [5] show polypharmacological features. In order to expand our knowledge and drug potentials, drug repurposing is a very productive method in drug discovery and development It is useful for identifying and classifying drugs based on their actions to multiple therapeutic targets (i.e., leading to better efficacy and/or safety) or their action to nontherapeutic targets (i.e., leading to adverse effects). We will discuss the difficulties of the drug discovery and the development process with respect to neuropsychiatric disorders and the extent of drug repurposing as an alternative approach in drug discovery and development

Challenges in Clinical Development for Neuropsychiatric Disorders

Promiscuity of Drug-Target Interactions

Other Aspects in Drug-Target Interactions

Drug Repurposing

NIHM PDSP Database and Receptoromics as Drug Repurposing Tool

H1 Oxytocin

Other Databases and Potential Tools for Drug Repurposing

Conclusions