Effect of pharmacologically selective antidepressants on serotonin uptake in rat platelets.
We tested a hypothesis that a long-term administration of antidepressants acting through different primary biochemical mechanisms is associated with changes in the platelet serotonin (5-hydroxytryptamine, 5-HT) transport. Laboratory rats were administered norepinephrine reuptake inhibitors (desipramine, maprotiline), selective 5-HT reuptake inhibitor (citalopram), reversible monoamine oxidase inhibitor (moclobemide), and lithium (inositol monophosphatase inhibitor among others) during a 4-week period. Apparent kinetic parameters of platelet 5-HT transport were analyzed. Significant decrease in apparent Michaelis constant (K(M)) was found after the administration of all tested antidepressants except for desipramine. There was certain increase in maximal velocity (V(max)) values following the administration of desipramine, maprotiline, and citalopram; however, the all V(max) changes were not significant. V(max)/K(M) ratio representing limiting permeability at low extracellular concentrations of 5-HT was systematically increased in all the tested drugs, but significant changes were occurred only in maprotiline- and citalopram-treated rats. Adaptive changes in platelet 5-HT transport induced by citalopram were opposite to the acute inhibitory effect of this drug on 5-HT transporter activity. An increase in limiting membrane permeability for 5-HT could be included in the common adaptive effect of the long-term administration of antidepressants that differ in pharmacologic selectivity.
Fisar
Z
Z
Department of Psychiatry, 1st Faculty of Medicine, Charles University, Ke Karlovu 11, 120 00 Prague 2, Czech Republic. zfisar@lf1.cuni.cz
Anders
M
M
Kalisová
L
L
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008571:Men; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000493:pharmacokinetics*
D000928:Antidepressive Agents; D012701:Serotonin