| Title |
Differential profile of typical, atypical and third generation antipsychotics at human 5-HT7a receptors coupled to adenylyl cyclase: detection of agonist and inverse agonist properties
|
|---|---|
| Published in |
Naunyn-Schmiedeberg's Archives of Pharmacology, September 2007
|
| DOI | 10.1007/s00210-007-0182-6 |
| Pubmed ID | |
| Authors |
Isabelle Rauly-Lestienne, Elisa Boutet-Robinet, Marie-Christine Ailhaud, Adrian Newman-Tancredi, Didier Cussac |
| Abstract |
5-HT(7) receptors are present in thalamus and limbic structures, and a possible role of these receptors in the pathology of schizophrenia has been evoked. In this study, we examined binding affinity and agonist/antagonist/inverse agonist properties at these receptors of a large series of antipsychotics, i.e., typical, atypical, and third generation compounds preferentially targeting D(2) and 5-HT(1A) sites. Adenylyl cyclase (AC) activity was measured in HEK293 cells stably expressing the human (h) 5-HT(7a) receptor isoform. 5-HT and 5-CT increased cyclic adenosine monophosphate level by about 20-fold whereas (+)-8-OH-DPAT, the antidyskinetic agent sarizotan, and the novel antipsychotic compound bifeprunox exhibited partial agonist properties at h5-HT(7a) receptors stimulating AC. Other compounds antagonized 5-HT-induced AC activity with pK (B) values which correlated with their pK (i) as determined by competition binding vs [(3)H]5-CT. The selective 5-HT(7) receptor ligand, SB269970, was the most potent antagonist. For antipsychotic compounds, the following rank order of antagonism potency (pK (B)) was ziprasidone > tiospirone > SSR181507 > or = clozapine > or = olanzapine > SLV-314 > SLV-313 > or = aripiprazole > or = chlorpromazine > nemonapride > haloperidol. Interestingly, pretreatment of HEK293-h5-HT(7a) cells with forskolin enhanced basal AC activity and revealed inverse agonist properties for both typical and atypical antipsychotics as well as for aripiprazole. In contrast, other novel antipsychotics exhibited diverse 5-HT(7a) properties; SLV-313 and SLV-314 behaved as quasi-neutral antagonists, SSR181507 acted as an inverse agonist, and bifeprunox as a partial agonist, as mentioned above. In conclusion, the differential properties of third generation antipsychotics at 5-HT(7) receptors may influence their antipsychotic profile. |
Mendeley readers
The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Brazil | 1 | 3% |
| Unknown | 30 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 5 | 16% |
| Other | 3 | 10% |
| Student > Doctoral Student | 3 | 10% |
| Professor | 3 | 10% |
| Student > Master | 3 | 10% |
| Other | 7 | 23% |
| Unknown | 7 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 8 | 26% |
| Medicine and Dentistry | 7 | 23% |
| Chemistry | 4 | 13% |
| Biochemistry, Genetics and Molecular Biology | 2 | 6% |
| Agricultural and Biological Sciences | 2 | 6% |
| Other | 1 | 3% |
| Unknown | 7 | 23% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 14 January 2013.
All research outputs
#7,452,489
of 22,785,242 outputs
Outputs from Naunyn-Schmiedeberg's Archives of Pharmacology
#347
of 1,723 outputs
Outputs of similar age
#24,877
of 70,008 outputs
Outputs of similar age from Naunyn-Schmiedeberg's Archives of Pharmacology
#1
of 5 outputs
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