The pharmacodynamic mechanisms of available antidepressant drugs have not yet clarified. Major depression is common and may more frequently occur for the first time in the eldery, and the incidence of thromboembolism is increased with advancing
of
age.
And many studies have shown an usefulness of platelet as models of monoaminergic neurons.
Therefore, this paper, deals with the anti-platelet activity of antidepressant drugs in view of the common action in platelet signal-transduction system of three antidepressant showing different modes of action.
The IC50s of amitriptyline, alprazolam, and rolipram were 1.39×10-4, 2.36×10-4,and 8.11×10-4M, respectlvely, and that of each of the reference drugs: sodium nitroprusside, chlorpromazine, and spermine were 1.26×10-6, 5.76×10-5, and
4.28×10-3
M.
Rolipram and alprazolam produced the significant increase of platelet cGMP level with slight cAMP increase, showing their selectivity on type II cGMP specific PDE.
Spermine and antidepressants, particularly used in this study induced the marked increase of platelet IP3 level with the anti-platelet and [Ca ++]I-decreasing activities.
These findings suggest that the mechanism of action of antidepressant drugs seems to be related with their enhancing property of the neuronal IP3-mediated signalling, and that the paradoxical mode of their actions on platelet metabolisms of
[Ca++]i
and
IP3 may be a clue of the uncovering of a new cellular [Ca++]i-regulating mode.
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