Citalopram Hydrobromide

Citalopram hydrobromide binds to the serotonin transporter (SERT), which is the major pharmacological target in the treatment of depression. In addition to the primary high-affinity binding site where citalopram blocks serotonin reuptake, a low-affinity allosteric site exists on SERT that influences the dissociation of citalopram from the primary site. The dissociation rate of [³H]S-citalopram from human SERT is retarded by serotonin and by several antidepressants when present in the dissociation buffer. Dissociation is most potently inhibited by S-citalopram, followed by R-citalopram, sertraline, serotonin, and paroxetine, with EC50 values of 3.6 μM and 19.4 μM for S- and R-citalopram respectively. The allosteric modulation is independent of temperature and sodium concentration.
Mutagenesis studies reveal that amino acid residues Met180, Tyr495, and Ser513 are important in mediating the allosteric effect and contribute to high-affinity binding at the primary site. The allosteric site is independent of the high-affinity binding site and may represent a new drug target.

Fig. 1 Concentration–response analysis of the allosteric effect of S-and R-citalopram on the dissociation rate of [³H]S-citalopram in complex with hSERT. (Chen F.; et al. 2005)

A thermoresponsive polymeric micelle system based on Pluronic F127 and Poloxamer 188 was developed for intranasal delivery of citalopram hydrobromide. The optimized formulation prepared by thin-film hydration method exhibited nanoscale micelle size of 31.41 nm, narrow size distribution with polydispersity index of 0.241, and lower critical solution temperature of approximately 31°C suitable for nasal administration. Encapsulation efficiency reached approximately 90% with a 95-fold increase in drug solubility. In vitro studies showed 25-fold faster drug release and four-fold enhanced nasal permeability. The formulation demonstrated appropriate biological and physical stability. This smart nanosystem offers a promising platform to overcome limitations of conventional citalopram administration by enhancing solubility, rapid release, and brain targeting through the nasal route.

Fig. 2 The formulation of citalopram-loaded thermosensitive polymeric micelles. (Rajab F.; et al. 2025)