The effect of tryptolines (1, 2, 3, 4-tetrahydro-β-carbolines) on monoamine metabolism and the platelet aggregation response in human platelets

Tryptolines (1, 2, 3, 4-tetrahydro-β-carbolines) are structurally related to 5-hydroxytryptamine. Using the human platelet preparation as a model of central serotoninergic neurons the action of various tryptolines on 5-hydroxytryptamine and epinephrine metabolism have been examined. All these compounds are competitive selective inhibitors of monoamine oxidase ‘type A’, 5-hydroxytryptamine being ‘type A’ substrate. 5-hydroxytryptoline and 5-methoxytryptoline are the most active monoamine oxidase inhibitors with IC₅₀ 0.5 μm and 1.5 μm respectively using 5-hydroxytryptamine as substrate. Tetrahydro-β-carbolines are also potent uptake inhibitors of 5-hydroxytryptamine and epinephrine; a significantly greater uptake inhibitory selectivity being shown for 5-hydroxytryptamine than epinephrine. Platelet aggregation response induced by 5-hydroxytryptamine, epinephrine and adenosine 5'-diphosphate are mediated by specific receptors on the platelet. Tetrahydro-β-carbolines by themselves do not induce platelet aggregation but are potent inhibitors of 5-hydroxytryptamine and epinephrineinduced aggregation. However, they are ineffective on aggregation induced by adenosine 5'-diphosphate. The comparison of the inhibition kinetics of tetrahydro-β-carbolines for 5-hydroxytryptamine and epinephrine uptake with that of the platelet aggregation response to these amines have shown that 5-hydroxymethtryptoline, methtryptoline, and tryptolin are poor inhibitors of uptake. However, 5-hydroxymethtryptoline and tryptoline are potent inhibitors of the aggregation response. It is suggested that tryptoline derivatives can distinguish between receptors for uptake and the platelet aggregation response to 5-hydroxytryptamine. In all respects 5-hydroxytryptoline and 5-methoxytryptoline showed greater pharmacological activity than the tryptoline and methtryptoline.Although the in vivo formation of tryptolines has been a matter of controversy, they have profound pharmacological activity. This is reflected in their actions described above. The results confirm what has been observed using rat brain preparations and would suggest that human platelets can be used as a model to study the action of these compounds on central serotoinergic neurons.