Affinities of fluoxetine, its enantiomers, and other inhibitors of serotonin uptake for subtypes of serotonin receptors.
The new antidepressant drugs, fluoxetine (and its enantiomers), citalopram, indalpine, paroxetine, and femoxetine show relatively weak affinities for 5-HT receptors as measured by radioligand binding to 5-HT-1(A,B,C and D), 5-HT-2, and 5-HT-3 subtypes. Fluoxetine and R(-)-fluoxetine, at near micromolar concentrations, inhibit 3H-mesulergine binding to 5-HT-1C receptors in bovine choroid plexus, and the R(-) enantiomer is 23 times more potent than the S(+) enantiomer. However, the near nanomolar potencies of these drugs as inhibitors of 5-HT uptake most likely account for their pharmacologic effects in animals.
Wong
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Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285.
Threlkeld
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Robertson
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D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects; D002417:Cattle; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism; D004873:Ergolines / Q000378:metabolism; D005473:Fluoxetine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013237:Stereoisomerism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000928:Antidepressive Agents; D004873:Ergolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D005473:Fluoxetine; D012701:Serotonin; C031649:mesulergine