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.
Rehavi
M
M
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Jerushalemi
Z
Z
Aviv
A
A
Laor
N
N
Podliszewski
E
E
Karp
L
L
Shavit
S
S
Weizman
R
R
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