Naslov
The effects of serotonin uptake inhibitors on platelet serotonin : From basic to clinical research

Autori
Muck-Šeler, Dorotea ; Pivac, Nela ; Šagud, Marina ; Mustapić, Maja ; Jakovljević, Miro

Vrsta, podvrsta i kategorija rada
Poglavlja u knjigama, znanstveni

Knjiga
Serotonin uptake inhibitors research

Urednik/ci
Columbus, Frank ; Anne C. Shirley

Izdavač
Nova Science Publishers

Grad
Haupauge (NY)

Godina
2005

Raspon stranica
29-53

ISBN
1-59454-338-0

Ključne riječi
blood platelets, platelet serotonin, serotonin uptake inhibitors, basic and clinical research

Sažetak
Numerous studies have shown that blood platelets might be used as an easy obtainable, peripheral model for the central serotonergic synaptosomes. Uptake, storage and release of serotonin (5-hydroxytryptamine, 5-HT) into platelets resemble the corresponding processes in the neurons. Moreover, receptors (5-HT2A, α 2-adrenergic) or binding sites (3H-imipramine, 3H-paroxetine) on the platelet membrane, and platelet monoamine oxidase (MAO), have pharmacological and kinetic characteristics similar to their counterparts in the neurons. These similarities, although provocative, define the framework for the studies using platelet 5-HT for the in vitro and in vivo investigations of the etiology and treatment of mental disorders. Serotonin reuptake inhibitors (SRIs) are compounds of different chemical structures that inhibit the active transport of 5-HT into neurons and platelets. The following order of relative potency of some SRIs for the in vitro 5-HT uptake inhibition was suggested: citalopram > fluvoxamine > amitriptyline >> trazodone > maprotiline. First SRIs used in clinical practice were traditional, tricyclic antidepressants (imipramine, amitriptyline, doxepine), with the less specific 5-HT uptake inhibition properties, and lower tolerability profile than the new, widely accepted selective SRIs (fluvoxamine, fluoxetine, paroxetine, sertraline). In vitro properties of SRIs on 5-HT uptake determine platelet 5-HT concentration in vivo. Clinical studies have shown that chronic treatment with amitriptyline, fluoxetine, clovoxamine, paroxetine, or sertraline markedly decrease platelet 5-HT concentrations. In contrast, chronic treatment with trazodone or maprotiline (weak inhibitors of the platelet 5-HT uptake) does not affect platelet 5-HT concentration. Although in vitro effect of SRIs on 5-HT uptake is rapid, the in vivo decrease in platelet 5-HT concentration appears only after 7 to 14 days of treatment. This delayed effect might be explained with the time of the turnover rate of platelets in the circulation, and antidepressant effect on 5-HT uptake into newly formed platelets. Clinical studies suggested that baseline platelet 5-HT concentration, platelet MAO activity, genetic variations in tryptophan hydroxylase or 5-HT transporter proteins might have some predictive value in the therapeutic response to SRIs. Recently, we have shown that increased pretreatment platelet 5-HT concentration might be associated to a nonresponse to paroxetine, and to a lesser extent, to sertraline treatment. These results provide a new insight for the use of platelets for the in vitro and in vivo assessments of the effects of SRIs.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA