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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2000-8-17
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pubmed:abstractText |
There is considerable interest in the use of drugs that selectively block presynaptic (somatodendritic) serotonin 5-HT(1A) receptors for the adjunctive treatment of major depressive disorder. The 5-HT(1A)/beta-adrenoceptor ligands (+/-)-pindolol, (-)-tertatolol, and (-)-penbutolol are currently under clinical investigation, and knowledge of their affinity at different populations of central 5-HT(1A) receptors is needed. Here we have determined the affinity of these drugs for presynaptic and postsynaptic 5-HT(1A) receptors in postmortem human and rat brain using receptor autoradiography and the selective 5-HT(1A) radioligand [(3)H]WAY-100635. The binding of [(3)H]WAY-100635 was specific and saturable and showed high affinity in the rat dorsal raphe nucleus and hippocampus (K(D) = 1.5-1.7 nM). In competition studies, the three compounds had nanomolar affinity and produced monophasic displacement of [(3)H]WAY-100635 binding in all regions of both species. (-)-Penbutolol and (-)-tertatolol had similar affinity for pre-and postsynaptic 5-HT(1A) receptors in both rat and human brain. However, in the human, but not the rat, the affinity of (+/-)-pindolol in dorsal raphe nucleus (K(i) = 8.9 +/- 1. 1 nM) was slightly but significantly higher than that in hippocampus (K(i) = 14.4 +/- 1.5 nM in CA1). In summary, our data show that (+/-)-pindolol, (-)-tertatolol, and (-)-penbutolol are all high-affinity ligands at native human and rat 5-HT(1A) receptors. (-)-Penbutolol and (-)-tertatolol do not discriminate between the pre- and postsynaptic 5-HT(1A) sites tested in either species, but (+/-)-pindolol showed a slightly higher affinity for the presynaptic site in human brain. Further work is needed to establish whether the latter difference is clinically relevant.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Arrhythmia Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Penbutolol,
http://linkedlifedata.com/resource/pubmed/chemical/Pindolol,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Propanolamines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Presynaptic,
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 Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Thiophenes,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/WAY 100635,
http://linkedlifedata.com/resource/pubmed/chemical/tertatolol
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-3042
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
75
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
755-62
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10899952-Aged,
pubmed-meshheading:10899952-Animals,
pubmed-meshheading:10899952-Anti-Arrhythmia Agents,
pubmed-meshheading:10899952-Autoradiography,
pubmed-meshheading:10899952-Brain,
pubmed-meshheading:10899952-Dentate Gyrus,
pubmed-meshheading:10899952-Female,
pubmed-meshheading:10899952-Hippocampus,
pubmed-meshheading:10899952-Humans,
pubmed-meshheading:10899952-Male,
pubmed-meshheading:10899952-Penbutolol,
pubmed-meshheading:10899952-Pindolol,
pubmed-meshheading:10899952-Piperazines,
pubmed-meshheading:10899952-Propanolamines,
pubmed-meshheading:10899952-Pyridines,
pubmed-meshheading:10899952-Radioligand Assay,
pubmed-meshheading:10899952-Raphe Nuclei,
pubmed-meshheading:10899952-Rats,
pubmed-meshheading:10899952-Rats, Sprague-Dawley,
pubmed-meshheading:10899952-Receptors, Presynaptic,
pubmed-meshheading:10899952-Receptors, Serotonin,
pubmed-meshheading:10899952-Receptors, Serotonin, 5-HT1,
pubmed-meshheading:10899952-Serotonin Antagonists,
pubmed-meshheading:10899952-Synapses,
pubmed-meshheading:10899952-Thiophenes,
pubmed-meshheading:10899952-Tritium
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pubmed:year |
2000
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pubmed:articleTitle |
Affinity of (+/-)-pindolol, (-)-penbutolol, and (-)-tertatolol for pre- and postsynaptic serotonin 5-HT(1A) receptors in human and rat brain.
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pubmed:affiliation |
University Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, England.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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