Matches in SemOpenAlex for { <https://semopenalex.org/work/W2002126868> ?p ?o ?g. }
- W2002126868 endingPage "95" @default.
- W2002126868 startingPage "88" @default.
- W2002126868 abstract "Inhibition of central α4β2 nAChRs by antidepressants, proposed to contribute to their clinical efficacy, was assessed for monoamine reuptake inhibitors (amitriptyline, nortriptyline, fluoxetine, sertraline, paroxetine, citalopram) by comparing projected human unbound brain drug concentrations (Cu,b) at therapeutic doses with concentrations that inhibit human α4β2 nAChRs in vitro. Inhibitory concentrations (IC50) were determined by patch clamp and ranged from 0.8-3.2 μM, except for nortriptyline (IC50 = 100 nM). Cu,b values were calculated from human unbound plasma drug concentrations (Cu,p) and rat-derived brain-to-plasma and extracellular fluid-to-plasma ratios for the unbound drug, which are near unity, due to much higher brain tissue binding than plasma protein binding of these drugs. Accordingly in humans, antidepressant Cu,b are projected to essentially equal Cu,p, with average values from 3-87 nM, which are 30-to-250-fold below their IC50 concentrations. Based on our model, monoaminergic antidepressants minimally inhibit central nAChRs and it is unlikely that α4β2 nAChR antagonism contributes to their antidepressant activity. Nortriptyline is an exception with a Cu,b that is 2-fold below its IC50, which is comparable to the nAChR antagonist (±)-mecamylamine, for which Cu,b is 4-fold below its IC50; both drugs will inhibit a substantial fraction of α4β2 nAChRs. The Cu,b of the α4β2 nAChR partial agonist varenicline, which has antidepressant-like activity in a murine model, is higher than its IC50 and varenicline is projected to cause ~70% inhibition of α4β2 nAChRs. Taken together these data may help explain the negative outcome of recent antidepressant augmentation trials with mecamylamine and the partial agonist CP-601927." @default.
- W2002126868 created "2016-06-24" @default.
- W2002126868 creator A5015738720 @default.
- W2002126868 creator A5024240272 @default.
- W2002126868 creator A5027341489 @default.
- W2002126868 creator A5051900776 @default.
- W2002126868 creator A5087068196 @default.
- W2002126868 creator A5087559454 @default.
- W2002126868 creator A5088302368 @default.
- W2002126868 date "2013-09-01" @default.
- W2002126868 modified "2023-09-30" @default.
- W2002126868 title "Therapeutic doses of antidepressants are projected not to inhibit human α4β2 nicotinic acetylcholine receptors" @default.
- W2002126868 cites W1503863057 @default.
- W2002126868 cites W1968217212 @default.
- W2002126868 cites W1972510096 @default.
- W2002126868 cites W1975263142 @default.
- W2002126868 cites W1979261550 @default.
- W2002126868 cites W1981086691 @default.
- W2002126868 cites W1982340856 @default.
- W2002126868 cites W1982429100 @default.
- W2002126868 cites W1985495870 @default.
- W2002126868 cites W1985905713 @default.
- W2002126868 cites W1990250882 @default.
- W2002126868 cites W1996732279 @default.
- W2002126868 cites W2000854227 @default.
- W2002126868 cites W2002604701 @default.
- W2002126868 cites W2012803743 @default.
- W2002126868 cites W2016292245 @default.
- W2002126868 cites W2018361785 @default.
- W2002126868 cites W2020194725 @default.
- W2002126868 cites W2024465317 @default.
- W2002126868 cites W2056272943 @default.
- W2002126868 cites W2059671050 @default.
- W2002126868 cites W2061166243 @default.
- W2002126868 cites W2066658868 @default.
- W2002126868 cites W2067319900 @default.
- W2002126868 cites W2073395907 @default.
- W2002126868 cites W2077857371 @default.
- W2002126868 cites W2081065619 @default.
- W2002126868 cites W2084800878 @default.
- W2002126868 cites W2094065556 @default.
- W2002126868 cites W2101520329 @default.
- W2002126868 cites W2106431483 @default.
- W2002126868 cites W2107757912 @default.
- W2002126868 cites W2116473479 @default.
- W2002126868 cites W2117024164 @default.
- W2002126868 cites W2119717973 @default.
- W2002126868 cites W2119786790 @default.
- W2002126868 cites W2122850765 @default.
- W2002126868 cites W2128527026 @default.
- W2002126868 cites W2131349644 @default.
- W2002126868 cites W2131930718 @default.
- W2002126868 cites W2134086028 @default.
- W2002126868 cites W2140788810 @default.
- W2002126868 cites W2143242847 @default.
- W2002126868 cites W2158900181 @default.
- W2002126868 cites W2165094621 @default.
- W2002126868 doi "https://doi.org/10.1016/j.neuropharm.2013.04.027" @default.
- W2002126868 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23639435" @default.
- W2002126868 hasPublicationYear "2013" @default.
- W2002126868 type Work @default.
- W2002126868 sameAs 2002126868 @default.
- W2002126868 citedByCount "14" @default.
- W2002126868 countsByYear W20021268682014 @default.
- W2002126868 countsByYear W20021268682015 @default.
- W2002126868 countsByYear W20021268682016 @default.
- W2002126868 countsByYear W20021268682017 @default.
- W2002126868 countsByYear W20021268682018 @default.
- W2002126868 countsByYear W20021268682019 @default.
- W2002126868 countsByYear W20021268682021 @default.
- W2002126868 crossrefType "journal-article" @default.
- W2002126868 hasAuthorship W2002126868A5015738720 @default.
- W2002126868 hasAuthorship W2002126868A5024240272 @default.
- W2002126868 hasAuthorship W2002126868A5027341489 @default.
- W2002126868 hasAuthorship W2002126868A5051900776 @default.
- W2002126868 hasAuthorship W2002126868A5087068196 @default.
- W2002126868 hasAuthorship W2002126868A5087559454 @default.
- W2002126868 hasAuthorship W2002126868A5088302368 @default.
- W2002126868 hasConcept C126322002 @default.
- W2002126868 hasConcept C134018914 @default.
- W2002126868 hasConcept C170493617 @default.
- W2002126868 hasConcept C185592680 @default.
- W2002126868 hasConcept C188987157 @default.
- W2002126868 hasConcept C202751555 @default.
- W2002126868 hasConcept C2775864247 @default.
- W2002126868 hasConcept C2775893369 @default.
- W2002126868 hasConcept C2775910092 @default.
- W2002126868 hasConcept C2776880047 @default.
- W2002126868 hasConcept C2777053506 @default.
- W2002126868 hasConcept C2777752497 @default.
- W2002126868 hasConcept C2779177272 @default.
- W2002126868 hasConcept C2779547902 @default.
- W2002126868 hasConcept C2780216858 @default.
- W2002126868 hasConcept C2780779033 @default.
- W2002126868 hasConcept C2780831388 @default.
- W2002126868 hasConcept C2781161787 @default.
- W2002126868 hasConcept C55493867 @default.
- W2002126868 hasConcept C71924100 @default.