Interaction between antidepressants and phosphoinositide signal transduction system in human platelets.
The present study was designed to evaluate the inhibitory effect of antidepressants on thrombin-induced phosphoinositide (PI) hydrolysis. Thrombin 5 units/ml induced a 100%-200% increase in platelet inositol phosphates (IPs) formation. This effect was inhibited in a dose-dependent manner by various heterocyclic antidepressants (IC50 40-170 mumol/L) The monoamine oxidase inhibitor, phenelzine, in concentrations up to 500 mumol/L, was devoid of inhibitory activity. The tricyclic antidepressants, (50 mumol/L) inhibited also thrombin-induced platelet aggregation by 32%-47%. No alteration in thrombin-induced IPs formation was detected in recovered major depressed patients (n = 15) maintained on clomipramine (75-150 mg/day). These results indicate that the heterocyclic antidepressants interfere with the thrombin-linked PI-signaling system. However, the inhibitory effect is achieved only in concentrations above the plasma concentrations obtained with therapeutic doses of these agents.
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
M
M
Rehavi
Z
Z
Jerushalemi
A
A
Aviv
N
N
Laor
E
E
Podliszewski
L
L
Karp
S
S
Shavit
R
R
Weizman
D000928:Antidepressive Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010716:Phosphatidylinositols / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013917:Thrombin / Q000494:pharmacology
D000928:Antidepressive Agents; D010716:Phosphatidylinositols; D013917:Thrombin