Serotonin is one of the most important neurotransmitters involved in the pathophysiology of depressive illness. The assessment of alteration of cerebral serotonin has been still controversial but interesting topic to study. Recently, increasing evidence has accumulated that the N100 amplitude slope reflects cerebral serotonin activity and treatment response of selective serotonin reuptake inhibitors (SSRIs). We report on two patients who showed abrupt mood changes and side effects after taking SSRI antidepressants. In both patients, aberrantly high N100 amplitude slopes were observed. Our cases suggest that the N100 amplitude slope may be a reliable indicator for predicting manic conversion and side effects in the SSRI treatment of depressive patients. Controlled studies are necessary to confirm whether a high N100 amplitude slope is a useful indicator of SSRI supersensitivity.
Antidepressive Agents ; Depression ; Humans ; Neurotransmitter Agents ; Serotonin ; Serotonin Uptake Inhibitors

Etifoxine (etafenoxine, Stresam(R)) is a non-benzodiazepine anxiolytic with an anticonvulsant effect. It was developed in the 1960s for anxiety disorders and is currently being studied for its ability to promote peripheral nerve healing and to treat chemotherapy-induced pain. In addition to being mediated by GABA(A)alpha2 receptors like benzodiazepines, etifoxine appears to produce anxiolytic effects directly by binding to beta2 or beta3 subunits of the GABA(A) receptor complex. It also modulates GABA(A) receptors indirectly via stimulation of neurosteroid production after etifoxine binds to the 18 kDa translocator protein (TSPO) of the outer mitochondrial membrane in the central and peripheral nervous systems, previously known as the peripheral benzodiazepine receptor (PBR). Therefore, the effects of etifoxine are not completely reversed by the benzodiazepine antagonist flumazenil. Etifoxine is used for various emotional and bodily reactions followed by anxiety. It is contraindicated in situations such as shock, severely impaired liver or kidney function, and severe respiratory failure. The average dosage is 150 mg per day for no more than 12 weeks. The most common adverse effect is drowsiness at the initial stage. It does not usually cause any withdrawal syndromes. In conclusion, etifoxine shows less adverse effects of anterograde amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes than those of benzodiazepines. It potentiates GABA(A) receptor-function by a direct allosteric effect and by an indirect mechanism involving the activation of TSPO. It seems promising that non-benzodiazepine anxiolytics including etifoxine will replenish shortcomings of benzodiazepines and selective serotonin reuptake inhibitors according to animated studies related to TSPO.
Amnesia, Anterograde ; Anti-Anxiety Agents ; Anticonvulsants ; Anxiety Disorders ; Anxiety* ; Benzodiazepines ; Flumazenil ; Humans ; Kidney ; Liver ; Mitochondrial Membranes ; Nerve Regeneration ; Neuralgia ; Neurotransmitter Agents ; Peripheral Nerves ; Peripheral Nervous System ; Psychomotor Performance ; Receptors, GABA-A ; Respiratory Insufficiency ; Serotonin Uptake Inhibitors ; Shock ; Sleep Stages

To explore novel monoamine reuptake inhibitor with antidepressant activity, a series of substituted aryl alkanol piperidine derivatives were designed and synthesized. All of them were new compounds, and their structures were confirmed with 1H NMR and HR-MS. The results showed that compounds 4, 5 and 8 displayed strong 5-HT, NA and DA reuptake inhibiting activities in vitro. Among the tested compounds, 4, 5 and 13 exhibited potent antidepressant activities in the mice forced swimming test. Compounds 4 and 5 have potent antidepressant activities and are worth further development.
Animals ; Antidepressive Agents ; chemical synthesis ; chemistry ; pharmacology ; Dopamine ; metabolism ; Male ; Mice ; Molecular Structure ; Motor Activity ; drug effects ; Neurotransmitter Uptake Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Norepinephrine ; metabolism ; Piperidines ; chemical synthesis ; chemistry ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism ; Structure-Activity Relationship ; Swimming ; Synaptosomes ; metabolism

Along with psychosocial factors of suicide, biological backgrounds of suicide are explored by extensive works mostly on biological markers, neurobiological models, genetic bases, and relationship with aggression and violence. The biology of suicide confers on neurotransmitters in central nervous system exploring metabolites, receptor binding affinities, neuroen-docrine challenge tests in brain, cerebrospinal fluid, blood and etc. The major concerns with suicide are focused mainly on serotomin system: low CSF-5-HIAA concentration, higher 5-HT2 receptor binding, and blunt prolactin response to fenfluramine. Postmortem study, in vivo study, genetic contributions, and some other issues such as suicidal methods, serum cholesteral, alcohol, and selective serotonin reuptake inhibitors are reviewed and discussed.
Aggression ; Biomarkers ; Biology ; Brain ; Central Nervous System ; Cerebrospinal Fluid ; Fenfluramine ; Models, Genetic ; Neurotransmitter Agents ; Pathology* ; Prolactin ; Psychology ; Serotonin Uptake Inhibitors ; Serotonin* ; Suicide* ; Violence*

The premenstrual syndrome is a common sense one: the cyclic appearance of one or more of a large constellation of symptoms just prior to menses, occuring to such a degree that lifestyle or work is affected, followed by a period of time entirely free of symptoms. Symptoms are believed to the result from interaction between central neurotransmitters and normal menstrual hormonal changes. Pharmacologic management to support efficacy includes selective serotonin reuptake inhibitors administered daily or premenstrually and serotonergic tricyclic antidepressants. Anxiolytics and potassium sparing diuretics have demonstrated mixed results in the literature. Hormonal therapy is available towards producing anovulation. There is a good clinical evidence for GnRH agonist with addback hormonal therapy. Oral contraceptive pills prevent ovulation and should be effective for the treatment of PMS. Treatment usually begins with lifestyle changes, over-thecounter medications. Physicians should be aware of the risks from many alternative therapies commonly touted in the popular press.
Anovulation ; Anti-Anxiety Agents ; Antidepressive Agents, Tricyclic ; Complementary Therapies ; Diuretics, Potassium Sparing ; Female ; Gonadotropin-Releasing Hormone ; Life Style ; Neurotransmitter Agents ; Ovulation ; Premenstrual Syndrome* ; Serotonin Uptake Inhibitors

Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients' heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity.
Biopsy ; Chest Pain ; Comorbidity ; Diagnosis ; Endoscopy ; Esophagus ; Female ; Gastrointestinal Diseases ; Heartburn ; Humans ; Hydrogen-Ion Concentration ; Hypersensitivity* ; Manometry ; Middle Aged ; Neurotransmitter Agents ; Proton Pumps ; Serotonin Uptake Inhibitors

Stroke patients often develop emotional disturbances including depression. The prevalence of this post-stroke depression (PSD) has been reported to range from 12 % to 64 %. The wide variation in the frequency of PSD may be related to methodological heterogeneity in items such as the criteria for depression, the timing of assessment, the sampled population and ethnicities. The relationship between the location of stroke and PSD remains also elusive. In addition to PSD, many of stroke patients reveal emotional incontinence, which is characterized by inappropriate or excessive laughing or crying. The incidence of and factors related to this post-stroke emotional incontinence (PSEI) also remain unclear. According to our study on out-patients with single, unilateral stroke, 18% had PSD and 34% had PSEI. Although both PSD and PSEI were related to motor dysfunction and location (anterior vs. posterior cortex) of the lesion, the latter was a stronger determinant for PSD. PSEI was more closely associated with subcortical strokes than was PSD. In addition, stroke patients may become easily irritated, impulsive, less generous, and prone to be angry or aggressive at others. This post stroke anger proneness (PSAP) was also common (32%) in our study. The PSAP was closely associated with the presence of PSEI. The lesion distribution was also similar. Both PSEI and PSAP respond well to serotonin reuptake inhibitors suggesting that these symptoms may be related to the alteration of an identical neurotransmitter (possibly serotonin) after a brain injury. Finally, post-stroke fatigue is common, occurring in 57% of the patients in our series. The post-stroke fatigue was related to the pre-stroke fatigue, physical disability and PSD. In summary, emotional disturbances such as depression, emotional incontinence, anger-proneness and fatigue are fairly common but under-recognized sequelae of stroke. These emotional disturbances decrease the quality of life of the patients and caregivers, and may affect the overall prognosis adversely. Therefore, these problems must be appropriately recognized and strategies to alleviate the symptoms should be developed based on the understanding of causative factors in individual patient.
Affective Symptoms ; Anger ; Anxiety* ; Brain Injuries ; Caregivers ; Crying ; Depression* ; Fatigue* ; Humans ; Incidence ; Neurotransmitter Agents ; Outpatients ; Population Characteristics ; Prevalence ; Prognosis ; Quality of Life ; Serotonin Uptake Inhibitors ; Stroke

Based on the pharmacophore information and the analysis of structure-activity relationship of SSRIs and SNRIs, a series of substituted aromatic heterocyclic arylamidine derivatives were designed and synthesized in order to search for lead compounds with dual activity. All of them were new compounds, and their structures were confirmed by 1H NMR and HRMS. Preliminary in vitro pharmacological tests showed that all target compounds exhibited 5-HT reuptake inhibitory activity and some compounds exhibited NE reuptake inhibitory activity. These aromatic heterocyclic arylamidine designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.
Amidines ; chemical synthesis ; chemistry ; pharmacology ; Animals ; Antidepressive Agents ; chemical synthesis ; pharmacology ; Drug Design ; Heterocyclic Compounds ; chemical synthesis ; chemistry ; pharmacology ; Neurotransmitter Uptake Inhibitors ; chemical synthesis ; pharmacology ; Norepinephrine ; metabolism ; Rats ; Rats, Wistar ; Serotonin ; metabolism ; Serotonin Uptake Inhibitors ; chemical synthesis ; pharmacology ; Structure-Activity Relationship ; Synapses ; metabolism

The present study was undertaken to explore the role of gamma-aminobutyric acid transporters in the neuropathic pain. On the chronic constriction injury (CCI) rats 4 doses (5, 10, 20, 40 microg in group N5, N10, N20, N40, respectively) of specific gamma-aminobutyric acid transporter-1 inhibitor NO-711 or normal saline (in group NS) were intrathecally administered before sciatic nerve ligation (pre-treatment) or at the third day after ligation (post-treatment). The paw withdrawl latency (PWL) from a noxious thermal stimulus and paw withdrawl mechanical threshold (PWMT) of von Frey filament was used as measure of thermal hyperalgesia and tactile allodynia respectively. The results demonstrated that post-treatment of NO-711 significantly suppressed thermal hyperalgesia and allodynia in CCI rats (P<0.05, P<0.01), the inhibitory effect lasted for 2 h (N40 group) and 4 h (N20 group) respectively. NO-711 inhibited thermal hyperalgesia induced by CCI in a dose-dependent manner. Intrathecal pretreatment with different doses of NO-711 delayed the occurrence of thermal hyperalgesia, but could not delay the emergence of allodynia induced by CCI. This study indicates that gamma-aminobutyric acid transporter inhibitor has anti-thermal hyperalgesia and anti-tactile allodynia effects in neuropathic rats.
Animals ; GABA Antagonists ; administration & dosage ; pharmacology ; Hyperalgesia ; drug therapy ; physiopathology ; Injections, Spinal ; Male ; Neurotransmitter Uptake Inhibitors ; administration & dosage ; pharmacokinetics ; Nipecotic Acids ; administration & dosage ; pharmacology ; Oximes ; administration & dosage ; pharmacology ; Pain ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Sciatic Neuropathy ; drug therapy ; physiopathology

OBJECTIVES: The purpose of this study was to suggest recommendations of antidepressant efficacy compared with placebo, difference in efficacy of antidepressants, and appropriate time of efficacy judgment in antidepressant therapy. METHODS: Using recommendations from 12 international and domestic clinical practice guidelines for depression, drawing of recommendation drafts, and peer review, the executive committee developed the guideline. RESULTS: Tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOI), selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRIs), norepinephrine and specific serotonergic antidepressants (NaSSAs), norepinephrine and dopamine reuptake inhibitors (NDRIs), and serotonin antagonist and reuptake inhibitors (SARIs) were strongly recommended as having antidepressant efficacy compared with placebo. Difference in efficacy of antidepressants was as follows. TCAs, MAOI, SSRI, SNRIs, and NaSSAs were strongly recommended, however, NDRIs, SARIs were weakly recommended. If there was no or minimal improvement with treatment, appropriate time of efficacy judgment in antidepressant therapy was estimated to be after two to four weeks. CONCLUSION: We hope that the results of this study will be helpful in encouraging the optimal treatment by understanding antidepressant efficacy compared with placebo, difference in efficacy of antidepressants, and appropriate time of efficacy judgment in antidepressant therapy.
Antidepressive Agents* ; Antidepressive Agents, Tricyclic ; Depression* ; Depressive Disorder, Major ; Dopamine Uptake Inhibitors ; Judgment* ; Monoamine Oxidase Inhibitors ; Norepinephrine ; Peer Review ; Serotonin ; Serotonin Uptake Inhibitors