F17464, a dopamine D3 receptor antagonist with relatively high D3 selectivity (70 fold vs D2 in vitro), exhibits an antipsychotic profile in preclinical studies, and therapeutic efficacy was demonstrated in a randomized placebo-controlled clinical trial in patients with schizophrenia (Bitter et al.
We investigated 15 single-nucleotide polymorphisms (SNPs) in DRD3 and four SNPs in BDNF for possible association with alcohol abuse or dependence in schizophrenia patients of European ancestry (N = 195).
In combination with previous studies, these results suggest that cariprazine has a unique pharmacological profile and distinct dopamine D3 receptor-dependent mechanism of action that may be beneficial in the treatment of schizophrenia, bipolar disorder, and major depressive disorder.
No association between dopamine D3 receptor gene rs6280" genes_norm="1814">Ser9Gly polymorphism (rs6280) and risk of schizophrenia: an updated meta-analysis.
We previously reported that YQA31 is a dopamine D3 receptor antagonist with modest 5-HT1A receptor affinity and that it exhibits antipsychotic properties in animal models of schizophrenia.
Expression of the dopamine D3 (DRD3) receptor was significantly increased in clozapine-treated schizophrenia and covaried significantly with differentiated T cell classes in the CD4+ lineage.
To assess the relationship between cognitive function, a proposed schizophrenia endophenotype, and two genetic polymorphisms related to dopamine function, catechol-O-methyl transferase (COMT) Val158Met and dopamine receptor 3 (DRD3) Ser9Gly.
The present study demonstrated that the mRNA expression levels of DRD3 in T lymphocytes were significantly different among controls, and in patients with psychotic disorder not otherwise specified (NOS) and schizophrenia/schizophreniform disorder.
Taken together, the results from the present study suggest that an interaction between BDNF and DRD3 may not play a major role in the risk for suicide attempt, though further studies, especially in SCZ, are required.
Antipsychotic haloperidol binding to the human dopamine D3 receptor: beyond docking through QM/MM refinement toward the design of improved schizophrenia medicines.
The dopamine D3 receptor (DRD3) gene has been implicated in schizophrenia, autism, and substance use-disorders and is related to emotion reactivity, executive functioning, and stress-responding, processes impaired in posttraumatic stress disorder (PTSD).
Eight SNPs were nominally associated with SZ in either case-control or family based analyses (p < 0.05, rs7631540 and rs2046496 in DRD3; rs363399 and rs10082463 in SLC18A2; rs4680, rs4646315 and rs9332377 in COMT). rs6271 at DBH was associated in both analyses.
Association was also evaluated by considering the polymorphisms as interactions; in this case, a likelihood ratio test (LRT) revealed evidence for association with schizophrenia in four polymorphism combinations: two DRD3*SNAP-25 combinations (rs6280*rs3746544 and rs6280*rs3746544, P=0.02), one ADRA2A*SNAP25 combination (rs1800544*rs3746544) and one ADRA2A*DBH combination (rs1800544*rs2519152).
A DRD3 gene polymorphism results in an S9G amino-acid change that has been associated with lower risk of schizophrenia, higher affinity for dopamine and some antipsychotics, and differential response to some antipsychotics.
In our Japanese case-control sample (43 with TD/157 without TD), we found no association between the DRD3Ser9Gly polymorphism in schizophrenia and TD (genotype: p=0.92; allele: p=1.00).
To identify whether functional variants of the D2-like receptors (DRD2, DRD3 and DRD4) confer risk of schizophrenia, we conducted a two-stage association study.
Overexpression of HERV-w env in human U251 glioma cells upregulated brain-derived neurotrophic factor (BDNF), an important schizophrenia-associated gene, neurotrophic tyrosine kinase receptor type 2 (NTRK2, also called TrkB), and dopamine receptor D3 and increased the phosphorylation of cyclic adenosine monophosphate response element-binding (CREB) protein.
Evaluation of (1) these known associations with DRD3, (2) the recent finding of Costas and colleagues that a haplotype containing Ser-9 is associated with protection from schizophrenia, and (3) an extant trait model of personality, leads to the hypothesis that an allele DRD3/Ser codes for trait aggression by Mendelian recessive inheritance.
Based on allele and genotype frequencies in both groups, we found no significant association of DRD3Ser9Gly polymorphisms and COMT (rs165656) with schizophrenia in Malays.