Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Catatonia and neuroleptic malignant syndrome (NMS) are uncommon disorders that can be life-threatening. Many researchers consider them as clinically divergent entities; however, they share similar and overlapping literature on causative agents, phenomenology, and treatment response. This hypothesis considers both disorders as a single entity that result from variable combinations of the following: 1) gamma-aminobutyric acid (GABA) hypoactivity at the GABAA receptor; 2) dopamine hypoactivity at the D2 receptor; 3) serotonin hyperactivity at the 5-HT1A receptor and hypoactivity at the 5-HT2A receptor; and 4) glutamate hypoactivity at the N-methyl-D-aspartate (NDMA) receptor. In this paper, evidence to support this hypothesis is limited to retrospective human studies of catatonia and NMS. The four components of the hypothesis are: 1) GABAA agonists have been shown to alleviate catatonia and NMS; 2) D2 antagonism is proportional to the relative likelihood of NMS and catatonia; 3) 5-HT1A agonism with 5-HT2A antagonism is implicated in catatonia and NMS; 4) NMDA receptor antagonists, such as phencyclidine and ketamine, reduce glutamate transmission. This hypothesis proposes that it is the interaction of these systems that prediposes, initiates, and maintains the twin syndromes of catatonia and NMS.
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PMID:The universal field hypothesis of catatonia and neuroleptic malignant syndrome. 1819 53

Major depression is a severe psychiatric syndrome with very high prevalence and socio-economic impact. Its pathophysiology is poorly known, yet several neurotransmitter systems and brain areas have been implicated. Selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) are most used antidepressant treatments. However, these drugs show slow onset of action and limited efficacy, making necessary the use of drug augmentation strategies or more aggressive interventions. Two important observations have emerged in recent years indicating that more rapid and effective antidepressant treatments are possible. Hence, the deep brain stimulation (DBS) of ventral anterior (subgenual) cingulate cortex (Cg25) evokes rapid mood improvements in subgroups of treatment-resistant depressive patients, likely mediated by a functional remodelling of cortico-limbic circuits. On the other hand, the non-competitive NDMA receptor antagonist ketamine can also evoke rapid (e.g., 2h) and persistent (up to 1 wk) improvements in some treatment-resistant patients. Moreover, recent preclinical observations indicate the antidepressant capacity of mGluR agents. Overall, this supports the usefulness of glutamatergic transmission as a new area in antidepressant drug development. On the monoamine side, new preclinical and clinical research should clarify the different roles played by 5-HT receptors in depression as well as the brain areas and circuits responsible for therapeutic improvement. This will lead to the synthesis of new agents blocking the serotonin (and possibly norepinephrine) transporter which will also activate or block 5-HT receptors playing respectively positive (e.g., postsynaptic 5-HT1A, 5-HT4) or negative (e.g., presynaptic 5-HT1A,/1B, 5-HT2A, 5-HT2C,5-HT3, etc.) roles in antidepressant effects.
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PMID:Developments in the field of antidepressants, where do we go now? 2370 76