Affinities of venlafaxine and various reuptake inhibitors for the serotonin and norepinephrine transporters.
In vitro radioligand binding studies were carried out in rat brain membranes to assess the affinity of various reuptake inhibitors for the serotonin (5-hydroxytryptamine, 5-HT) and the norepinephrine transporters using the selective ligands [3H]cyanoimipramine and [3H]nisoxetine, respectively. The selective 5-HT reuptake inhibitors paroxetine, indalpine and fluvoxamine displayed a high affinity for the 5-HT transporter, whereas the norepinephrine reuptake inhibitor desipramine had a high affinity for the norepinephrine transporter. Duloxetine, a dual 5-HT and norepinephrine reuptake inhibitor, displayed a high affinity for both the 5-HT and the norepinephrine transporters. Interestingly, venlafaxine, a dual 5-HT and norepinephrine reuptake inhibitor, displayed only a moderate affinity for the 5-HT transporter (Ki = 74 nM) and a very low affinity for the norepinephrine transporter (Ki = 1.26 microM). The relatively low affinities of venlafaxine contrast with its potent in vivo 5-HT and norepinephrine reuptake blocking properties. These results raise the possibility that the in vivo effects on the 5-HT and norepinephrine reuptake observed with venlafaxine may not be mediated solely by its binding to the [3H]cyanoimipramine and [3H]nisoxetine binding sites.
Neurobiological Psychiatry Unit, McGill University, Montréal, Canada.
J C
JC
Béïque
N
N
Lavoie
C
C
de Montigny
G
G
Debonnel
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D003511:Cyclohexanols / Q000378:metabolism*; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000378:metabolism; D007099:Imipramine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D014179:Neurotransmitter Uptake Inhibitors / Q000378:metabolism*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism; D027981:Symporters; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D002352:Carrier Proteins; D003511:Cyclohexanols; D005473:Fluoxetine; D007099:Imipramine; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D014179:Neurotransmitter Uptake Inhibitors; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012701:Serotonin; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D027981:Symporters; D000069470:Venlafaxine Hydrochloride; C493226:Slc6a2 protein, rat; C493232:Slc6a4 protein, rat; C024316:cianopramine; C011386:nisoxetine