The differences in specificity between certain drugs
The side effects produced by many of the antidepressant drugs arise from their ability to block muscarinic cholinergic receptors, H1 histamine receptors and α1-adrenergic receptors. The affinity (Ki) of a drug for a specific receptor is defined as the concentration of drug needed to occupy 50% of the available receptors; the lower the Ki value, the more potently the receptor is blocked. Many antidepressants block muscarinic cholinergic receptors causing side effects such as; dry mouth, blurred vision, constipation and urinary retention. The tricyclic antidepressants (TCAs) as a class block these receptors more potently than other types of antidepressant, and they are all associated with these side effects. Postural hypotension is associated with blockade of α1-adrenoceptors and this side effect is often seen with TCAs due to their relatively high affinity at these receptors. Histamine H1 receptor blockade causes sedation and drowsiness. Given the high affinity of mirtazapine for H1 receptors it is not surprising that many patients taking this medication report drowsiness and sedation. These side effects are not frequently observed with selective 5-HT re-uptake transporters, reboxetine or venlafaxine due to low affinity at H1 receptors.
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References
J Clin Psychiatry 1997;58(Suppl. 6):9–25.