Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present paper attempts to place the clinical use of clonidine in gynecology in a broadened perspective against the most recent advances in neuropsychopharmacology. From this review emerges the concept that clonidine, by means of its action in the central nervous system, probably affects mechanisms of crucial significance in psychosomatic symptomatology, involving the balance between attention to the external versus the internal environment. Since brain NE systems such as the one originating in the LC influence or reach vast regions of the CNS and not only cardiovascular centres, any malfunction of the LC system, whether induced by, for example, drug addiction or hormonal factors, will affect a number of functions of the individual, particularly responses to stress, and, as we understand, cardiovascular and vegetative reactivity. At present we can hypothesize that a damping or, perhaps, stabilization of the responsiveness of brain NE systems may be a fundamental mechanism of action of clonidine in this regard. As a consequence of this discussion the use of clonidine in other disorders with a clear psychosomatic component, such as the irritable bowel syndrome as well as premenstrual tension, appear to be quite interesting future avenues to explore.
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PMID:Clonidine treatment in vegetative dysfunction--experimental rationales. 386 Oct 64

The 5-HT(3) receptor is a ligand-gated ion channel widely distributed in the central and peripheral nervous systems. Many selective 5-HT(3) receptor antagonists have been developed; animal studies with such compounds suggested their potential therapeutic value in combating emesis and a wide range of CNS diseases including anxiety, schizophrenia, drug dependence and Alzheimer's disease. Their successful introduction as anti-emetics, with irritable bowel syndrome emerging as a further indication have partially fulfilled this initial promise. However, the CNS area has been less productive and, to date, no selective 5-HT(3) receptor antagonist has been approved for use in a CNS disease.
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PMID:5-HT(3) receptor antagonists. 1113 47

The 5-Hydroxytryptamine3 (5-HT3) receptor is a member of the cys-loop family of ligand gated ion channels, of which the nicotinic acetylcholine receptor is the prototype. All other 5-HT receptors identified to date are metabotropic receptors. The 5-HT3 receptor is present in the central and peripheral nervous systems, as well as a number of non-nervous tissues. As an ion channel that is permeable to the cations, Na(+), K(+), and Ca(2+), the 5-HT3 receptor mediates fast depolarizing responses in pre- and post-synaptic neurons. As such, 5-HT3 receptor antagonists that are used clinically block afferent and efferent synaptic transmission. The most well established physiological roles of the 5-HT3 receptor are to coordinate emesis and regulate gastrointestinal motility. Currently marketed 5-HT3 receptor antagonists are indicated for the treatment of chemotherapy, radiation, and anesthesia-induced nausea and vomiting, as well as irritable bowel syndrome. Other therapeutic uses that have been explored include pain and drug addiction. The 5-HT3 receptor is one of a number of receptors that play a role in mediating nausea and vomiting, and as such, 5-HT3 receptor antagonists demonstrate the greatest anti-emetic efficacy when administered in combination with other drug classes.
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PMID:Therapeutics of 5-HT3 receptor antagonists: current uses and future directions. 2135 41

Despite major advances in our understanding of the brain using traditional neuroscience, reliable and efficacious treatments for drug addiction have remained elusive. Hence, the time has come to utilize novel approaches, particularly those drawing upon contemporary advances in fields outside of established neuroscience and psychiatry. Put another way, the time has come for a paradigm shift in the addiction sciences. Apropos, a revolution in the area of human health is underway, which is occurring at the nexus between enteric microbiology and neuroscience. It has become increasingly clear that the human microbiota (the vast ecology of bacteria residing within the human organism), plays an important role in health and disease. This is not surprising, as it has been estimated that bacteria living in the human body (approximately 1kg of mass, roughly equivalent to that of the human brain) outnumber human cells 10 to 1. While advances in the understanding of the role of microbiota in other areas of human health have yielded intriguing results (e.g., Clostridium difficile, irritable bowel syndrome, autism, etc.), to date, no systematic programs of research have examined the role of microbiota in drug addiction. The current hypothesis, therefore, is that gut dysbiosis plays a key role in addictive disorders. In the context of this hypothesis, this paper provides a rationale for future research to target the "gut-brain axis" in addiction. A brief background of the gut-brain axis is provided, along with a series of hypothesis-driven ideas outlining potential treatments for addiction via manipulations of the "ecology within."
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PMID:Targeting the ecology within: The role of the gut-brain axis and human microbiota in drug addiction. 2737 61

Corticotropin-releasing factor (CRF) is an important neuropeptide hormone which controls the body's overall response to stress. It plays a crucial role in regulating the behavioral, cardiovascular, immune and gastrointestinal systems. Over-activation of the CRF system has been implicated in many disorders including anxiety, depression, drug addiction, hypertension, Irritable Bowel Syndrome (IBS), peptic ulcers, inflammation and others. Thus, binding of CRF to its receptors is an attractive target to develop new medications which aim at treating ailments associated with chronic stress. Numerous small-molecule non-peptide CRF receptor antagonists were developed and many are in various stages in clinical trials. Many showed great promise in treatment of anxiety, depression, peptic ulcers, inflammation, IBS and drug addiction. In our recent previous work, the development of two series of pyrimidine and fused pyrimidine CRF antagonists were described. In continuation of our efforts in this direction, in the current manuscript, the synthesis of a third series of CRF receptor antagonists is described. The binding affinities of select compounds for the type 1 receptor of CRF (CRF1R) were determined and compared to a standard CRF antagonist drug antalarmin. A lead compound was identified and further evaluated by measuring its effect on the inhibition of the agonist-stimulated accumulation of second messengers.
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PMID:Synthesis of 2-imino and 2-hydrazono thiazolo[4,5-d]pyrimidines as corticotropin releasing factor (CRF) antagonists. 2875 Mar 12