PET Occupancy and Competition in Translational Medicine and CNS Drug Development

Cumming, Paul; Gründer, Gerhard

doi:10.1016/b978-0-12-803161-2.00010-2

Cited by 1 publication

(1 citation statement)

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“…PET is a useful technique for receptor imaging and occupancy by investigational drugs in the living animal and human brain [ 159 , 160 , 161 ]. Due to the structural similarity of D3Rs and D2Rs, their similar localization in various brain areas (with higher density of D2Rs), the high affinity of DA for D3R, the in vivo imaging of D3R by PET have long been hindered by the lack of high affinity and selective PET ligands with good kinetic profile (i.e., low metabolic liability and good CNS penetration) for this receptor.…”

Section: D3r Ligandsmentioning

confidence: 99%

Neuronal Dopamine D3 Receptors: Translational Implications for Preclinical Research and CNS Disorders

et al. 2021

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Dopamine (DA), as one of the major neurotransmitters in the central nervous system (CNS) and periphery, exerts its actions through five types of receptors which belong to two major subfamilies such as D1-like (i.e., D1 and D5 receptors) and D2-like (i.e., D2, D3 and D4) receptors. Dopamine D3 receptor (D3R) was cloned 30 years ago, and its distribution in the CNS and in the periphery, molecular structure, cellular signaling mechanisms have been largely explored. Involvement of D3Rs has been recognized in several CNS functions such as movement control, cognition, learning, reward, emotional regulation and social behavior. D3Rs have become a promising target of drug research and great efforts have been made to obtain high affinity ligands (selective agonists, partial agonists and antagonists) in order to elucidate D3R functions. There has been a strong drive behind the efforts to find drug-like compounds with high affinity and selectivity and various functionality for D3Rs in the hope that they would have potential treatment options in CNS diseases such as schizophrenia, drug abuse, Parkinson’s disease, depression, and restless leg syndrome. In this review, we provide an overview and update of the major aspects of research related to D3Rs: distribution in the CNS and periphery, signaling and molecular properties, the status of ligands available for D3R research (agonists, antagonists and partial agonists), behavioral functions of D3Rs, the role in neural networks, and we provide a summary on how the D3R-related drug research has been translated to human therapy.

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Section: D3r Ligandsmentioning

confidence: 99%