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Mendeley readers
Attention Score in Context
| Title |
Neuropsychopharmacology of JNJ-55308942: evaluation of a clinical candidate targeting P2X7 ion channels in animal models of neuroinflammation and anhedonia
|
|---|---|
| Published in |
Neuropsychopharmacology, July 2018
|
| DOI | 10.1038/s41386-018-0141-6 |
| Pubmed ID | |
| Authors |
Anindya Bhattacharya, Brian Lord, Jan-Sebastian Grigoleit, Yingbo He, Ian Fraser, Shannon N. Campbell, Natalie Taylor, Leah Aluisio, Jason C. O’Connor, Mariusz Papp, Christa Chrovian, Nicholas Carruthers, Timothy W. Lovenberg, Michael A. Letavic |
| Abstract |
Emerging data continues to point towards a relationship between neuroinflammation and neuropsychiatric disorders. ATP-induced activation of P2X7 results in IL-1β release causing neuroinflammation and microglial activation. This study describes the in-vitro and in-vivo neuropharmacology of a novel brain-penetrant P2X7 antagonist, JNJ-55308942, currently in clinical development. JNJ-55308942 is a high-affinity, selective, brain-penetrant (brain/plasma of 1) P2X7 functional antagonist. In human blood and in mouse blood and microglia, JNJ-55308942 attenuated IL-1β release in a potent and concentration-dependent manner. After oral dosing, the compound exhibited both dose and concentration-dependent occupancy of rat brain P2X7 with an ED50 of 0.07 mg/kg. The P2X7 antagonist (3 mg/kg, oral) blocked Bz-ATP-induced brain IL-1β release in conscious rats, demonstrating functional effects of target engagement in the brain. JNJ-55308942 (30 mg/kg, oral) attenuated LPS-induced microglial activation in mice, assessed at day 2 after a single systemic LPS injection (0.8 mg/kg, i.p.), suggesting a role for P2X7 in microglial activation. In a model of BCG-induced depression, JNJ-55308942 dosed orally (30 mg/kg), reversed the BCG-induced deficits of sucrose preference and social interaction, indicating for the first time a role of P2X7 in the BCG model of depression, probably due to the neuroinflammatory component induced by BCG inoculation. Finally, in a rat model of chronic stress induced sucrose intake deficit, JNJ-55308942 reversed the deficit with concurrent high P2X7 brain occupancy as measured by autoradiography. This body of data demonstrates that JNJ-55308942 is a potent P2X7 antagonist, engages the target in brain, modulates IL-1β release and microglial activation leading to efficacy in two models of anhedonia in rodents. |
X Demographics
The data shown below were collected from the profiles of 8 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 1 | 13% |
| Egypt | 1 | 13% |
| Mexico | 1 | 13% |
| Unknown | 5 | 63% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 63% |
| Scientists | 2 | 25% |
| Practitioners (doctors, other healthcare professionals) | 1 | 13% |
Mendeley readers
The data shown below were compiled from readership statistics for 66 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 66 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 12 | 18% |
| Student > Ph. D. Student | 11 | 17% |
| Student > Bachelor | 10 | 15% |
| Student > Doctoral Student | 4 | 6% |
| Student > Master | 3 | 5% |
| Other | 7 | 11% |
| Unknown | 19 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 10 | 15% |
| Immunology and Microbiology | 5 | 8% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 8% |
| Medicine and Dentistry | 4 | 6% |
| Biochemistry, Genetics and Molecular Biology | 3 | 5% |
| Other | 13 | 20% |
| Unknown | 26 | 39% |
Attention Score in Context
This research output has an Altmetric Attention Score of 11. 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 27 November 2023.
All research outputs
#3,279,381
of 25,523,622 outputs
Outputs from Neuropsychopharmacology
#1,651
of 5,191 outputs
Outputs of similar age
#62,108
of 340,029 outputs
Outputs of similar age from Neuropsychopharmacology
#33
of 83 outputs
Altmetric has tracked 25,523,622 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,191 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 19.3. This one has gotten more attention than average, scoring higher than 68% 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 340,029 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 81% of its contemporaries.
We're also able to compare this research output to 83 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 61% of its contemporaries.