혈소판 Cyclic Nucleotide, Inositol Trisphosphate 및 [Ca^(++)]_(i)의 응집반응성 변동에 대한 항우울성 약물의 영향

초록

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 antidepressants showing different modes of action. The IC_(50)s of amitriptyline alprazolam. and rolipram were 1.39×10^(-4), 2.63×10^(-4), and 8.11×10^(-4)M. respectively, 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 typeⅡ cGMP-specific PDE. Spermine and antidepressants, particularly used in this study induced the marked increase of platelet IP_(3) 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 IP_(3)-mediated signalling. and that the paradoxical mode of their actions on platelet metabolisms of [Ca^(++)]_(i) and IP_(3) may be a clue of the uncovering of a new cellular [Ca^(++)]_(i)-regulating mode.