| Title |
Dual- and Triple-Acting Agents for Treating Core and Co-morbid Symptoms of Major Depression: Novel Concepts, New Drugs
|
|---|---|
| Published in |
Neurotherapeutics, January 2009
|
| DOI | 10.1016/j.nurt.2008.10.039 |
| Pubmed ID | |
| Authors |
Mark J Millan |
| Abstract |
The past decade of efforts to find improved treatment for major depression has been dominated by genome-driven programs of rational drug discovery directed toward highly selective ligands for nonmonoaminergic agents. Selective drugs may prove beneficial for specific symptoms, for certain patient subpopulations, or both. However, network analyses of the brain and its dysfunction suggest that agents with multiple and complementary modes of action are more likely to show broad-based efficacy against core and comorbid symptoms of depression. Strategies for improved multitarget exploitation of monoaminergic mechanisms include triple inhibitors of dopamine, serotonin (5-HT) and noradrenaline reuptake, and drugs interfering with feedback actions of monoamines at inhibitory 5-HT(1A), 5-HT(1B) and possibly 5-HT(5A) and 5-HT(7) receptors. Specific subsets of postsynaptic 5-HT receptors mediating antidepressant actions are under study (e.g., 5-HT(4) and 5-HT(6)). Association of a clinically characterized antidepressant mechanism with a nonmonoaminergic component of activity is an attractive strategy. For example, agomelatine (a melatonin agonist/5-HT(2C) antagonist) has clinically proven activity in major depression. Dual neurokinin(1) antagonists/5-HT reuptake inhibitors (SRIs) and melanocortin(4) antagonists/SRIs should display advantages over their selective counterparts, and histamine H(3) antagonists/SRIs, GABA(B) antagonists/SRIs, glutamatergic/SRIs, and cholinergic agents/SRIs may counter the compromised cognitive function of depression. Finally, drugs that suppress 5-HT reuptake and blunt hypothalamo-pituitary-adrenocorticotrophic axis overdrive, or that act at intracellular proteins such as GSK-3beta, may abrogate the negative effects of chronic stress on mood and neuronal integrity. This review discusses the discovery and development of dual- and triple-acting antidepressants, focusing on novel concepts and new drugs disclosed over the last 2 to 3 years. |
Mendeley readers
The data shown below were compiled from readership statistics for 216 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 2 | <1% |
| Spain | 2 | <1% |
| United States | 2 | <1% |
| Australia | 1 | <1% |
| Czechia | 1 | <1% |
| Canada | 1 | <1% |
| Netherlands | 1 | <1% |
| Japan | 1 | <1% |
| Malaysia | 1 | <1% |
| Other | 0 | 0% |
| Unknown | 204 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 35 | 16% |
| Researcher | 26 | 12% |
| Student > Master | 26 | 12% |
| Student > Bachelor | 22 | 10% |
| Student > Doctoral Student | 16 | 7% |
| Other | 44 | 20% |
| Unknown | 47 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 51 | 24% |
| Psychology | 25 | 12% |
| Agricultural and Biological Sciences | 24 | 11% |
| Chemistry | 17 | 8% |
| Neuroscience | 16 | 7% |
| Other | 35 | 16% |
| Unknown | 48 | 22% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. 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 30 December 2023.
All research outputs
#5,452,627
of 25,394,764 outputs
Outputs from Neurotherapeutics
#571
of 1,307 outputs
Outputs of similar age
#28,957
of 183,354 outputs
Outputs of similar age from Neurotherapeutics
#3
of 13 outputs
Altmetric has tracked 25,394,764 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,307 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.2. This one has gotten more attention than average, scoring higher than 51% 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 183,354 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 78% of its contemporaries.
We're also able to compare this research output to 13 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.