In Vivo Systems Response Profiling and Multivariate Classification of CNS Active Compounds: A Structured Tool for CNS Drug Discovery.
ACS Chem Neurosci
; 8(4): 785-797, 2017 04 19.
Article
en En
| MEDLINE
| ID: mdl-27997108
ABSTRACT
This paper describes the application of in vivo systems response profiling in CNS drug discovery by a process referred to as the Integrative Screening Process. The biological response profile, treated as an array, is used as major outcome for selection of candidate drugs. Dose-response data, including ex vivo brain monoaminergic biomarkers and behavioral descriptors, are systematically collected and analyzed by principal component analysis (PCA) and partial least-squares (PLS) regression, yielding multivariate characterization across compounds. The approach is exemplified by assessing a new class of CNS active compounds, the dopidines, compared to other monoamine modulating compounds including antipsychotics, antidepressants, and procognitive agents. Dopidines display a distinct phenotypic profile which has prompted extensive further preclinical and clinical investigations. In summary, in vivo profiles of CNS compounds are mapped, based on dose response studies in the rat. Applying a systematic and standardized work-flow, a database of in vivo systems response profiles is compiled, enabling comparisons and classification. This creates a framework for translational mapping, a crucial component in CNS drug discovery.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fármacos del Sistema Nervioso Central
/
Evaluación Preclínica de Medicamentos
Límite:
Animals
Idioma:
En
Revista:
ACS Chem Neurosci
Año:
2017
Tipo del documento:
Article
País de afiliación:
Suecia