The differences in specificity between certain drugs
Different types of antidepressants inhibit the re-uptake of noradrenaline and 5-HT with different potency (IC50 value). The lower the IC50 value, the more potent the drug. Secondary amine tricyclic antidepressants (TCAs), such as desipramine and nortriptyline, are relatively selective inhibitors of noradrenaline re-uptake. For example, desipramine is about 150-fold more potent as an inhibitor of noradrenaline re-uptake (IC50 = 2) than 5-HT re-uptake (IC50 = 300). In vitro, tertiary amine TCAs, such as amitriptyline and imipramine, are slightly more potent inhibitors of noradrenaline re-uptake than 5-HT re-uptake; however, they do not exhibit any selectivity in vivo. As their class names imply, noradrenaline re-uptake inhibitors (NARIs) and selective serotonin re-uptake inhibitors (SSRIs) are selective inhibitors of noradrenaline and 5-HT re-uptake, respectively. The SSRI paroxetine inhibits re-uptake of 5-HT (IC50 = 1) about 70-fold more potently than noradrenaline re-uptake (IC50 = 70). Although classed as a ‘nonselective’ reu-ptake inhibitor, in vitro venlafaxine is a more potent blocker of 5-HT re-uptake than noradrenaline reuptake. Mirtazapine is a very weak inhibitor at both noradrenaline and 5-HT re-uptake sites. It exerts its effects by antagonising α2-adrenoceptors.
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References
J Clin Psychiatry 1997;58(Suppl. 6):9–25.