Increasing pharmacological knowledge about human neurological and psychiatric disorders through functional neuroimaging and its application in drug discovery

TY - JOUR

T1 - Increasing pharmacological knowledge about human neurological and psychiatric disorders through functional neuroimaging and its application in drug discovery

AU - Nathan, Pradeep J.

AU - Phan, K. Luan

AU - Harmer, Catherine J.

AU - Mehta, Mitul A.

AU - Bullmore, Edward T.

PY - 2014/2

Y1 - 2014/2

N2 - Functional imaging methods such as fMRI have been widely used to gain greater understanding of brain circuitry abnormalities in CNS disorders and their underlying neurochemical basis. Findings suggest that: (1) drugs with known clinical efficacy have consistent effects on disease relevant brain circuitry, (2) brain activation changes at baseline or early drug effects on brain activity can predict long-term efficacy; and (3) fMRI together with pharmacological challenges could serve as experimental models of disease phenotypes and be used for screening novel drugs. Together, these observations suggest that drug related modulation of disease relevant brain circuitry may serve as a promising biomarker/method for use in drug discovery to demonstrate target engagement, differential efficacy, dose-response relationships, and prediction of clinically relevant changes.

AB - Functional imaging methods such as fMRI have been widely used to gain greater understanding of brain circuitry abnormalities in CNS disorders and their underlying neurochemical basis. Findings suggest that: (1) drugs with known clinical efficacy have consistent effects on disease relevant brain circuitry, (2) brain activation changes at baseline or early drug effects on brain activity can predict long-term efficacy; and (3) fMRI together with pharmacological challenges could serve as experimental models of disease phenotypes and be used for screening novel drugs. Together, these observations suggest that drug related modulation of disease relevant brain circuitry may serve as a promising biomarker/method for use in drug discovery to demonstrate target engagement, differential efficacy, dose-response relationships, and prediction of clinically relevant changes.

KW - SOCIAL ANXIETY DISORDER

KW - NK1 RECEPTOR ANTAGONISM

KW - CUE-INDUCED ACTIVATION

KW - HEALTHY-VOLUNTEERS

KW - BRAIN ACTIVATION

KW - AMYGDALA REACTIVITY

KW - ANTERIOR CINGULATE

KW - TREATMENT RESPONSE

KW - PREFRONTAL CORTEX

KW - VENTRAL STRIATUM

U2 - 10.1016/j.coph.2013.11.009

DO - 10.1016/j.coph.2013.11.009

M3 - Article

SN - 1471-4892

VL - 14

SP - 54

EP - 61

JO - Current Opinion in Pharmacology

JF - Current Opinion in Pharmacology

ER -