Visualizing Pharmacological Activities of Antidepressants: A Novel Approach

Abstract

Antidepressants have different receptor binding profiles, which are related to therapeutic action and adverse drug reactions. We constructed a model to classify antidepressants on the basis of their binding properties of most common transporter-and receptor sites. Receptor binding was quantified by calculating receptor occupancy for the 5-HT (serotonin) reuptake transporter, norepinephrinic reuptake transporter, 5-HT 2C -receptor, M 3 -receptor, H 1 -receptor and 1 -receptor. To identify groups of antidepressants that show similar patterns of receptor occupancy for different receptors, hierarchical cluster analysis (HCA) and principle component analysis (PCA) were used. In addition, to visualize (a)symmetry between binding profiles of antidepressants, radar plots were constructed. On the basis of both analyses, four clusters of antidepressants which exert similar pharmacological properties were identified. Potentially, this model could be a helpful tool in medical practice and may be used as a prediction model for adverse effects of drugs entering the market.

Glucose dysregulation associated with antidepressant agents: an analysis of 17 published case reports

“…In that study, hyperglycemia was most pronounced in antidepressants with binding properties for the 5-HT 2c receptor (serotonin), H 1 -receptor (histamine), and norepinephrinic reuptake transporter [9,10]. In contrast, hypoglycemia was most pronounced in antidepressants with binding properties for the serotonin reuptake transporter [9,10]. In another study, antidepressants with a high affinity for the serotonin reuptake transporter were associated with a trend toward increased risk for hypoglycemia (OR = 1.37; 95% CI: 0.71-2.62) [8].…”

“…Although no clear pattern between antidepressant class (i.e., tricyclic antidepressants [TCAs], selective serotonin reuptake inhibitors [SSRI], serotonin-norepinephrine reuptake inhibitors [SNRIs], and other antidepressants) and hyperglycemia or hypoglycemia was observed in this review of case reports, the study by Derijks et al showed that the propensity to cause hyperglycemia or hypoglycemia was dependent on the pharmacological properties of individual antidepressant agents (see ''Appendix'') rather than a class effect [49,50]. In that study, hyperglycemia was most pronounced in antidepressants with binding properties for the 5-HT 2c receptor (serotonin), H 1 -receptor (histamine), and norepinephrinic reuptake transporter [9,10]. In contrast, hypoglycemia was most pronounced in antidepressants with binding properties for the serotonin reuptake transporter [9,10].…”

“…Given the limitations of case reports in establishing causation and the ambivalence in observational studies regarding the association between antidepressants and glucose dysregulation, more research is needed to establish whether changes in glucose regulation following antidepressant therapy are as a result of medications or changes in mood and lifestyle. Adapted from Derijks et al [10] NaSSA norepinephrine and serotonin specific with alpha-2 antagonist properties, NDRI norepinephrine dopamine reuptake inhibitor, NRI selective norepinephrine reuptake inhibitor, TCA tricyclic antidepressant, TeCA tetracyclic antidepressant, SARI serotonin-2 antagonist/reuptake inhibitor, SNRI serotonin-norepinephrine reuptake inhibitor, SSRI selective serotonin reuptake inhibitor a Six receptor/transporter sites: 5-HT (serotonin) reuptake transporter, norepinephrine reuptake transporter, 5-HT 2c receptor, M 3 -receptor (muscarinic), H 1 -receptor (histamine), alpha-1 receptor b Brand name nefazodone (Serzone) discontinued in 2004 due to cases of hepatotoxicity. Generic nefazodone is still on the market.…”

“…In both studies, hypoglycemia was most associated with antidepressants with affinity for the serotonin reuptake transporter (i.e., selective serotonin reuptake inhibitors and clomipramine) [8][9][10]. On the other hand, hyperglycemia was most associated with antidepressants with high binding affinity for the 5-HT 2c receptor (serotonin), H 1 -receptor (histamine), and norepinephrine reuptake transporter (i.e., amitriptyline, doxepin, imipramine, maprotiline, nortriptyline, mianserin, mirtazapine) [8,10] (see ''Appendix'').…”

“…Classification of selected antidepressant agents on high binding affinity for receptor/transporter sites as proposed by Derijks et al[10] …”