Designing new treatments for depression and anxiety.
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.
Chen
Zhengming
Z
DOV Pharmaceutical Inc, Somerset, NJ 08873-4185, USA. zchen@dovpharm.com
Yang
Ji
J
Tobak
Anne
A
D000928:Antidepressive Agents / Q000737:chemistry / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003863:Depression / Q000188:drug therapy*; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D014179:Neurotransmitter Uptake Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D011963:Receptors, GABA-A / Q000737:chemistry / Q000627:therapeutic use
D000928:Antidepressive Agents; D014179:Neurotransmitter Uptake Inhibitors; D011963:Receptors, GABA-A