Dopamine D3 Receptor Antagonists as Potential Therapeutics for the Treatment of Neurological Diseases

Abstract

D3 receptors represent a major focus of current drug design and development of therapeutics for dopamine-related pathological states. Their close homology with the D2 receptor subtype makes the development of D3 selective antagonists a challenging task. In this review, we explore the relevance and therapeutic utility of D3 antagonists or partial agonists endowed with multireceptor affinity profile in the field of central nervous system disorders such as schizophrenia and drug abuse. In fact, the peculiar distribution and low brain abundance of D3 receptors make them a valuable target for the development of drugs devoid of motor side effects classically elicited by D2 antagonists. Recent research efforts were devoted to the conception of chemical templates possibly endowed with a multi-target profile, especially with regards to other G-protein-coupled receptors (GPCRs). A comprehensive overview of the recent literature in the field is herein provided. In particular, the evolution of the chemical templates has been tracked, according to the growing advancements in both the structural information and the refinement of the key pharmacophoric elements. The receptor/multireceptor affinity and functional profiles for the examined compounds have been covered, together with their most significant pharmacological applications.

Highly Selective Dopamine D3 Receptor Antagonists with Arylated Diazaspiro Alkane Cores

“…1 These receptors are classified into two subtypes, D 1 -like and D 2 -like, based on sequence identity and similarity in signal transduction. The D 2 -like dopamine D 3 receptor (D 3 R) is a protein of interest for various neurological and neuropsychiatric disorders including schizophrenia, Parkinson’s disease, dementia, anxiety and depression.…”

A utilização do Método de Rorschach no diagnóstico diferencial da Esquizofrenia e Transtorno Dissociativo de Identidade

“…Assim, observa-se que o diagnóstico menos preciso de um e de outro transtorno pode levar o curso da patologia a resultados bem distintos, conforme o tratamento adotado: na esquizofrenia, ele inclui a farmacologia, com a prescrição de antipsicóticos que inibem muito os receptores da dopamina das vias dopaminérgicas; neurolépticos, indicados para pacientes que não respondem aos antipsicóticos convencionais ou que sofrem efeitos colaterais indesejáveis. Também há indicação de psicoterapia, com a finalidade, entre outras, de interromper a perda da capacidade mental, preservando o contato com a realidade (Amato, Beasley, Hahn, & Vernon, 2016;Kar, Barreto, & Chandavarkar, 2016;Maramai et al, 2016).…”

Development of molecular tools based on the dopamine D3 receptor ligand FAUC 329 showing inhibiting effects on drug and food maintained behavior

“…22, 23 There is an increasing evidence that the dopamine D 3 receptor may also be involved in seeking behavior of reinforcing effects of natural rewards like food. 24 Support was provided by the finding that the D 3 receptor antagonist SB-277011A produced a significant decrease in food intake and responses for food in an operant task in Zucker obese and lean rats. 25 Further evidence of the involvement of D 3 receptors in modulating food-seeking behavior was demonstrated by a study of Nathan et al 26 , which examined the effects of the D 3 receptor antagonist GSK598809 on attentional bias to rewarding food cues in overweight to obese individuals.…”