Abstract
Identifying novel marine-derived neuroactive chemicals with therapeutic potential is difficult due to inherent complexities of the central nervous system (CNS), our limited understanding of the molecular foundations of neuro-psychiatric conditions, as well as the limited applications of effective high-throughput screening models that recapitulate functionalities of the intact CNS. Furthermore, nearly all neuro-modulating chemicals exhibit poorly characterized pleiotropic activities often referred to as polypharmacology. The latter renders conventional target-based in vitro screening approaches very difficult to accomplish. In this context, chemobehavioural phenotyping using innovative small organism models such as planarians and zebrafish represent powerful and highly integrative approaches to study the impact of new chemicals on central and peripheral nervous systems. In contrast to in vitro bioassays aimed predominantly at identification of chemicals acting on single targets, phenotypic chemobehavioural analysis allows for complex multi-target interactions to occur in combination with studies of polypharmacological effects of chemicals in a context of functional and intact milieu of the whole organism. In this review, we will outline recent advances in high-throughput chemobehavioural phenotyping and provide a future outlook on how those innovative methods can be utilized for rapidly screening and characterizing marine-derived compounds with prospective applications in neuropharmacology and psychosomatic medicine.
Highlights
Contemporary drug discovery pipelines for most pathological conditions commonly employ molecular target-based screening of compound libraries. This approach is often referred to as reverse chemical biology/pharmacology and necessitates understanding of the mechanisms underlying the pathogenesis of a given disease with very well defined potential molecular targets for drug design and optimization (Figure 1) [1,2,3,4]
In recent years the above drug discovery paradigm has been plagued by some significant failures, especially in development of drugs for central nervous system (CNS) such as neurodegenerative and neuropsychiatric diseases [6,7,8,9]
Since the behavioural phenotyping is an essential part of neuro-active drug discovery but cannot be efficiently performed on rodent in vivo models, there is a need for new models [31,32,33,34,35]
Summary
Contemporary drug discovery pipelines for most pathological conditions commonly employ molecular target-based screening of compound libraries. In a cellular or physiological phenotype such as inhibiting cell death of dopaminergic neurons in Complicating the complexity of CNS drug discovery, the majority of neuro-modulating chemicals exhibit poorly characterized pleiotropic activities often referred to as polypharmacology [6,11,20] The latter involves activation of many targets and renders molecular target-based in vitro screening approaches practically impossible to accomplish at our current stage of neurobiological knowledge [11,20,21,22]. Recent analysis of success rates in various clinical trials of small-molecule drugs has demonstrated that to date significantly more drugs were discovered and approved for clinical use using a phenotypic screening approach rather than molecular target-based approach [1,2,3,4,16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
