Source:http://linkedlifedata.com/resource/pubmed/id/11166513
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
2001-2-22
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| pubmed:abstractText |
Augmentation of selective serotonin reuptake inhibitors (SSRIs) therapy by the 5-HT(1A) receptor agent pindolol may reduce the delay between initiation of antidepressant treatment and clinical response. This hypothesis is based on the ability of pindolol to block 5-HT(1A) autoreceptors in the dorsal raphe nuclei (DRN) and to potentiate the increase in 5-HT transmission induced by SSRIs. However, placebo-controlled clinical studies of pindolol augmentation of antidepressant therapy have reported inconsistent results. Here, we evaluated the occupancy of 5-HT(1A) receptors during treatment with pindolol controlled release (CR) in nine healthy volunteers with Positron Emission Tomography and [11C]WAY 100635. Subjects were studied four times: at baseline, following one week of pindolol CR 7.5 mg/day (4 and 10 hrs post dose), and following one dose of pindolol CR 30 mg(4 hrs post dose). Occupancy of the DRN was 40 +/- 29% on scan 2, 38 +/- 26% on scan 3, and 64 +/- 15% on scan 4. The average occupancy in all other regions was significantly lower at each doses (18 +/- 5% on scan 2, 12 +/- 3% on scan 3, and 42 +/- 4% on scan 4). These results suggest that the blockade in the DRN reached in clinical studies (7.5 mg/day) might be too low and variable to consistently augment the therapeutic effect of SSRIs. However, these data indicate that pindolol exhibits in vivo selectivity for the DRN 5-HT(1A) autoreceptors. As DRN selectivity is desirable for potentiation of 5-HT function, this observation represents an important proof of concept for the development of 5-HT(1A) agents in this application.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antidepressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Pindolol,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Neurotransmitter,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin, 5-HT1,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Uptake Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/WAY 100635
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
|
| pubmed:issn |
0893-133X
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| pubmed:author |
pubmed-author:Abi-DarghamAA,
pubmed-author:CaltabianoSS,
pubmed-author:CowleyHH,
pubmed-author:HashimotoTT,
pubmed-author:HuangYY,
pubmed-author:HwangDD,
pubmed-author:KentJJ,
pubmed-author:LaruelleMM,
pubmed-author:MaliziaAA,
pubmed-author:MannJ JJJ,
pubmed-author:MartinezDD,
pubmed-author:MawlawiOO,
pubmed-author:ParseyR VRV,
pubmed-author:ShinaRR,
pubmed-author:SimpsonNN,
pubmed-author:SlifsteinMM,
pubmed-author:Van HeertumRR
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| pubmed:issnType |
Print
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| pubmed:volume |
24
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
209-29
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| pubmed:dateRevised |
2011-5-18
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| pubmed:meshHeading |
pubmed-meshheading:11166513-Adult,
pubmed-meshheading:11166513-Antidepressive Agents,
pubmed-meshheading:11166513-Brain,
pubmed-meshheading:11166513-Humans,
pubmed-meshheading:11166513-Kinetics,
pubmed-meshheading:11166513-Magnetic Resonance Imaging,
pubmed-meshheading:11166513-Male,
pubmed-meshheading:11166513-Mood Disorders,
pubmed-meshheading:11166513-Pindolol,
pubmed-meshheading:11166513-Piperazines,
pubmed-meshheading:11166513-Pyridines,
pubmed-meshheading:11166513-Raphe Nuclei,
pubmed-meshheading:11166513-Receptors, Neurotransmitter,
pubmed-meshheading:11166513-Receptors, Serotonin,
pubmed-meshheading:11166513-Receptors, Serotonin, 5-HT1,
pubmed-meshheading:11166513-Serotonin Uptake Inhibitors,
pubmed-meshheading:11166513-Synaptic Transmission,
pubmed-meshheading:11166513-Tomography, Emission-Computed
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| pubmed:year |
2001
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| pubmed:articleTitle |
Differential occupancy of somatodendritic and postsynaptic 5HT(1A) receptors by pindolol: a dose-occupancy study with [11C]WAY 100635 and positron emission tomography in humans.
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| pubmed:affiliation |
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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