| Title |
Dopamine D3 receptor antagonism—still a therapeutic option for the treatment of schizophrenia
|
|---|---|
| Published in |
Naunyn-Schmiedeberg's Archives of Pharmacology, November 2012
|
| DOI | 10.1007/s00210-012-0806-3 |
| Pubmed ID | |
| Authors |
Gerhard Gross, Karsten Wicke, Karla U. Drescher |
| Abstract |
The potential of D(3) receptor antagonism to treat positive, negative, and cognitive symptoms of schizophrenia is reviewed on the basis of preclinical results and preliminary clinical data. Dopamine D(3) receptors are expressed in mesencephalic, limbic, and cortical areas relevant to psychotic and cognitive symptoms of schizophrenia. As expected, selective dopamine D(3) receptor antagonists are not effective in antipsychotic animal models, reflecting D(2) receptor antagonism. However, selective D(3) receptor antagonists affect electrical activity of dopamine neurons in the ventral tegmental area similar to atypical antipsychotics, counteract effects produced by NMDA glutamate receptor blockade, and enhance cortical dopamine and acetylcholine in microdialysis. In contrast to dopamine D(2) receptor antagonists, D(3) antagonists positively influence a variety of social and cognitive behaviors in rodents, including tests representing cognitive flexibility and executive function, which are both impaired in schizophrenia patients. Despite considerable affinity for D(3) receptors, the second-generation antipsychotics clozapine, risperidone, and olanzapine when administered to patients with schizophrenia seem not to occupy D(3) receptors sufficiently to derive any conclusion on a D(3)-mediated therapeutic benefit. ABT-925, the first selective D(3) receptor antagonist, was recently studied in patients with schizophrenia. It produced cognitive signals but did not achieve sufficient D(3) receptor occupancy to test the hypothesis that D(3) receptor antagonism is of therapeutic value to treat symptoms of schizophrenia. Based on mechanistic and experimental considerations and due to the fact that D(3) receptor antagonism can inhibit extrapyramidal symptoms and produce neither anhedonia nor metabolic adverse effects, the development and clinical testing of newer D(3) receptor antagonists with high potency at D(3) receptors, enabling sufficient receptor occupancy, is highly warranted. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 99 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 2% |
| Chile | 1 | 1% |
| Australia | 1 | 1% |
| Mexico | 1 | 1% |
| Iceland | 1 | 1% |
| Denmark | 1 | 1% |
| Poland | 1 | 1% |
| Unknown | 91 | 92% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 15 | 15% |
| Researcher | 14 | 14% |
| Student > Master | 9 | 9% |
| Other | 8 | 8% |
| Professor > Associate Professor | 7 | 7% |
| Other | 22 | 22% |
| Unknown | 24 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 17 | 17% |
| Psychology | 15 | 15% |
| Agricultural and Biological Sciences | 11 | 11% |
| Neuroscience | 7 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 5% |
| Other | 13 | 13% |
| Unknown | 31 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 August 2019.
All research outputs
#6,917,125
of 22,685,926 outputs
Outputs from Naunyn-Schmiedeberg's Archives of Pharmacology
#320
of 1,720 outputs
Outputs of similar age
#53,126
of 183,492 outputs
Outputs of similar age from Naunyn-Schmiedeberg's Archives of Pharmacology
#3
of 8 outputs
Altmetric has tracked 22,685,926 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 1,720 research outputs from this source. They receive a mean Attention Score of 4.0. This one has done well, scoring higher than 81% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 183,492 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 8 others from the same source and published within six weeks on either side of this one. This one has scored higher than 5 of them.