Figure 2

Promiscuity maps. A. SSRIs interact with multiple classes of ion channels, and increases neurosteroid synthesis (by directly modulating a rate limiting enzyme activity), in addition to its activity on the serotonin reuptake transporter (SERT). Neurosteroids are themselves promiscuous modulators of ion channels, and some of these interactions are shown (dotted lines from purple box). The impact of increasing serotonin is manifest at potentially any of seven categories of serotonin receptor (each with several subtypes), spanning ionotropic, metabotropic, varying localization, and different second messenger cascades. B. Promiscuity map of direct interactions of SSRIs with various metabotropic receptors and transporters (polygons), as well as ion channels (rectangles) including K channels (blue), Ca channels (green), LGICs (yellow). Distance from the central SSRI node approximates the log-scaled affinity of SSRI for the various targets. Concentric dotted circles reflect 3 orders of concentration magnitude (0.1, 1, and 10 μM). Therapeutic SSRI concentration in vivo is between 1-10 μM, that is, between the middle and outer circle. This figure was generated using CellDesigner software.