[Towards an understanding of the molecular mechanisms underlying the pharmacological treatments of XXXX ].

@entity1 @entity935 @entity71 @entity889 @entity4678 @entity1154 @entity750 @entity2661 @entity1063 @entity2727
@entity2727 and the @entity889 are the most frequently used medications for treating @entity71 ( @entity71 ). These medications modulate both @entity1063 as well as @entity935 . @entity2727 is a pure blocker of the @entity1063 and @entity935 transporters. The @entity889 also block reuptake of both @entity2661 , but they also release all three @entity1154 , @entity1063 , @entity935 , and @entity750 , from presynaptic vesicles. @entity889 are the most robust agents in increasing synaptic @entity935 levels, since they do so regardless of the endogenous level of the relevant neurons. Stimulant-evoked synaptic increases of @entity935 have been demonstrated in the striatum in @entity1 , but pharmacologic effects are likely relevant to therapeutic action in other regions, particularly the prefrontal cortex. Blockade of noradrenergic reuptake in the prefrontal cortex may also indirectly increase prefrontal @entity935 levels, but there is also evidence that noradrenergic effects are mediated by alpha-2a noradrenergic receptors. A recent study in non- @entity1 primates found that @entity2727 and @entity4678 both increased the efficiency of prefrontal pyramidal neurons, but via distinct mechanisms. @entity2727 decreased non-specific signals, i.e., neuronal noise, via D1 receptors. By contrast, @entity4678 increased the strength of specific signals via activation of alpha-2 receptors. These findings, although in non- @entity1 primates, suggest that combinations of agents working on these complementary systems (D1 and alpha-2a) may be worth considering and evaluating rigorously in @entity1 with @entity71 with sub-optimal responses to monotherapy.
