Advances in the treatment of depression

Abstract

Summary: Depression is a highly prevalent and disabling condition associated with significant morbidity and mortality. Currently available treatments for depression include tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, various atypical antidepressants, and electroconvulsive therapy. Although these treatments are effective, a significant number of patients do not respond or achieve sustained remission despite aggressive management. Advances in the neurobiology of depression have suggested a number of novel targets for antidepressant treatment. Based on an improved understanding of the neurobiology of depression, several novel pharmacologic and nonpharmacologic interventions are being developed. Pharmacologic developments include CRF antagonists, glucocorticoid receptor antagonists, substance P receptor antagonists, NMDA glutamate receptor antagonists, transdermal selegiline, so-called "triple" reuptake inhibitors, and augmentation of typical antidepressant medications with atypical antipsychotics. Nonpharmacologic advances have largely involved focal brain stimulation techniques including vagus nerve stimulation, transcranial magnetic stimulation, magnetic seizure therapy, and deep brain stimulation. For the most part, the data on these treatments are preliminary, and more study is needed to clarify their potential clinical benefit. However, it is clear that further study of the neurobiology of depression will continue to provide a rationale for developing innovative targets for antidepressant therapies.

5-Chloro-2-(2′-((dimethylamino)methyl)-4′-iodophenylthio)benzenamine: a new serotonin transporter ligand

“…In the ADAM (2) series of compounds, we have recently prepared two derivatives, the O-bridged, OADAM (3) and C-bridged, 4, and measured the kinetics of the brain uptake of the 125 I labeled compounds in rats [44] (Table 1). The specific hypothalamus uptake of C-bridged, [ 125 I]4, was inferior to that of OADAM (3) and ADAM (2). It was found that OADAM (3) consistently displayed a higher uptake in the hypothalamus (between 60-240 minutes post iv injection) than that of ADAM (2).…”

“…The specific hypothalamus uptake of C-bridged, [ 125 I]4, was inferior to that of OADAM (3) and ADAM (2). It was found that OADAM (3) consistently displayed a higher uptake in the hypothalamus (between 60-240 minutes post iv injection) than that of ADAM (2). The specific uptake of OADAM (3) in the hypothalamus exhibited the highest target to non-target ratio (hypothalamus/cerebellum, HY/CB, was 5.3 at 240 minutes post iv injection).…”

“…The associations between serotonergic function and depression have been well documented [4][5][6]. It is commonly held that patients with major depression experience changes in the serotonergic neuronal transmission function in the brain [1][2][3]. A series of newer antidepressants preferentially increase 5-HT (serotonin) transmission by inhibiting serotonin reuptake.…”

“…Biphenylthiol derivatives, [ 123 I] IDAM (1) [41] and [ 123 I]ADAM (2) [39,42], have been evaluated as potential agents for SPECT because there are several unique benefits associated with using this core structure (Table 1). Biphenylthiol contains no optical center and the synthesis is relatively simple.…”

“…Our laboratory has previously reported IDAM (1) and ADAM (2). In the ADAM (2) series of compounds, we have recently prepared two derivatives, the O-bridged, OADAM (3) and C-bridged, 4, and measured the kinetics of the brain uptake of the 125 I labeled compounds in rats [44] (Table 1).…”