Designing new treatments for depression and anxiety.
ABSTRACT Depression and anxiety are disabling disorders that affect many individuals. Drugs that interfere with the reuptake and/or metabolism of biogenic amines have been used to treat depression for more than four decades. An important development in the treatment of depression has been the emergence of triple reuptake inhibitors (SNDRIs), which inhibit the reuptake of serotonin, norepinephrine and dopamine. Preclinical and clinical research indicates that drugs inhibiting the reuptake of all of these neurotransmitters can produce a more rapid onset of action and greater efficacy than traditional antidepressants. Allosteric modulation of GABAA receptors can produce anxiolytic, sedative/hypnotic and anesthetic effects, presumably from enhancing the inhibitory neurotransmission of GABAA through a facilitation of receptor function. Benzodiazepines have been used with great success as anxiolytics, but the use of these drugs is limited because of their addictive potential and sedative side effects. This feature review discusses the design and synthesis of antidepressants based on the monoamine hypothesis of depression, and presents the current status of research on GABAA receptor modulators as a potential treatment for anxiety disorders.
SourceAvailable from: Francisco Garcia-Oscos
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ABSTRACT: Growing evidence suggests that pharmacotherapy may be beneficial for some patients with binge eating disorder (BED), an eating disorder characterized by repetitive episodes of uncontrollable consumption of abnormally large amounts of food without inappropriate weight loss behaviors. In this paper, we provide a brief overview of BED and review the rationales and data supporting the effectiveness of specific medications or medication classes in treating patients with BED. We conclude by summarizing these data, discussing the role of pharmacotherapy in the BED treatment armamentarium, and suggesting future areas for research.Therapeutics and Clinical Risk Management 01/2012; 8:219-41. DOI:10.2147/TCRM.S25574 · 1.34 Impact Factor
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ABSTRACT: Abstract The ratio between synaptic inhibition and excitation (sI/E) is a critical factor in the pathophysiology of neuropsychiatric disease. We recently described a stress-induced interleukin-6 dependent mechanism leading to a decrease in sI/E in the rodent temporal cortex. The aim of the present study was to determine whether a similar mechanism takes place in the prefrontal cortex, and to elaborate strategies to prevent or attenuate it. We used aseptic inflammation (single acute injections of lipopolysaccharide, LPS, 10 mg/Kg) as stress model, and patch-clamp recording on a prefrontal cortical slice preparation from wild-type rat and mice, as well as from transgenic mice in which the inhibitor of IL-6 trans-signaling sgp130Fc was produced in a brain-specific fashion (sgp130Fc mice). The anti-inflammatory reflex was activated either by vagal nerve stimulation or peripheral administration of the nicotinic α7 receptor agonist PHA543613. We found that the IL-6-dependent reduction in prefrontal cortex synaptic inhibition was blocked in sgp130Fc mice, or -in wild-type animals- upon application sgp130Fc. Similar results were obtained by activating the “anti-inflammatory reflex” -a neural circuit regulating peripheral immune response- by stimulation of the vagal nerve or through peripheral administration of the α7 nicotinic receptor agonist PHA543613. Our results indicate that the prefrontal cortex is an important potential target of IL-6 mediated trans-signaling, and suggest a potential new avenue in the treatment of a large class of hyperexcitable neuropsychiatric conditions, including epilepsy, schizophrenic psychoses, anxiety disorders, autism spectrum disorders, and depression.Brain Behavior and Immunity 01/2015; 43:149–158. DOI:10.1016/j.bbi.2014.07.020 · 6.13 Impact Factor