Effects of washing procedure on platelets pretreated with serotonin uptake inhibitors in vitro: low Ki values predict long-lasting inhibition of serotonin uptake in vivo.
The effect of a washing procedure on serotonin (5-HT) uptake in vitro was investigated using human platelets pretreated with nine 5-HT uptake inhibitors and various Ki values to confirm the assumption that a drug with high affinity for the 5-HT uptake site would be hardly removed and have a long-lasting effect in vivo. Among the drugs tested, those with low Ki values, such as clomipramine, duloxetine and paroxetine, inhibited 5-HT uptake even after removal from the medium, while those with high Ki values such as amitriptyline, desipramine, imipramine, mianserin, trazodone, and zimelidine were easily removed by washing. The results indicated that low Ki values might be proportionally related to the long-lasting binding of drugs to the 5-HT uptake site. The results also suggested that the threshold Ki value which could separate 5-HT uptake inhibitors with a probable long-lasting effect in vivo from those without the effect would be between 5 nM and 42 nM.
Ishigooka
J
J
Department of Psychiatry, Kitasato University School of Medicine, Sagamihara, Japan.
Kasahara
T
T
Nagata
E
E
Murasaki
M
M
Miura
S
S
D000928:Antidepressive Agents / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism*; D002478:Cells, Cultured; D002997:Clomipramine / Q000378:metabolism* / Q000494:pharmacology; D003864:Depression, Chemical; D000068736:Duloxetine Hydrochloride; D006801:Humans; D017374:Paroxetine / Q000378:metabolism* / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism* / Q000494:pharmacology; D013876:Thiophenes / Q000378:metabolism* / Q000494:pharmacology
D000928:Antidepressive Agents; D002997:Clomipramine; D000068736:Duloxetine Hydrochloride; D017374:Paroxetine; D011985:Receptors, Serotonin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes