Improved potency of escitalopram on the human serotonin transporter: demonstration of an ex vivo assay technique.
The potency of escitalopram ("Lexapro," s-citalopram, LU-26-054) was compared with that of racemic citalopram ("Celexa") using plasma samples from drug-treated normal controls applied to an assay of human serotonin [5-hydroxytryptamine (5-HT)] transport inhibition in blood platelets. Samples were available for both 4-hour and 24-day drug administration. The data indicated that 5-HT transport inhibition was fully manifest for each drug within 4 hours of administration, without significant increase in platelet transport inhibition by 24-day treatment. In addition, a dose-response relationship could be seen for escitalopram and citalopram with increasing 5-HT transport inhibition observed with increasing dose. It was evident from the data that escitalopram was significantly more potent than its racemate in inhibiting human platelet 5-HT transport. Thirty milligrams of escitalopram approximated the effect of 60 mg of racemic citalopram, and similarly, 10 mg of escitalopram approximated that of 20 mg of its racemate. This is the first demonstration of escitalopram's pharmacodynamic effect on the human 5-HT transporter. The results demonstrate its superior potency at the human 5-HT transporter site.
Rausch
Jeffrey L
JL
Department of Psychiatry, Veterans Administration, The Medical College of Georgia, Augusta, GA 30912-3800, USA. jeffreyr@mail.mcg.edu
Corley
Katina M
KM
Hobby
H Mac
HM
D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects*; D015283:Citalopram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000187:drug effects*; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins / Q000187:drug effects*; D012701:Serotonin / Q000097:blood; D050486:Serotonin Plasma Membrane Transport Proteins
D018687:Antidepressive Agents, Second-Generation; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D015283:Citalopram; D012701:Serotonin