Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The five subtypes of dopaminergic receptors exhibit different transduction, cerebral localization, regulation, pharmacological, and physiological roles, explaining their multiple pathophysiological implications in different neuropsychiatric conditions which result, at least in part from anomalous dopaminergic neurotransmission: Parkinson's disease, schizophrenia, addiction, migraine, mode disorders, Gilles de la Tourette disease, hyperactivity syndrome with attention deficit. The wide range of pharmacological implications explains the diversity of the therapeutic approaches perspectives for development of new drugs for these neuropsychiatric conditions.
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PMID:[Central dopaminergic receptors (Part II): pathophysiological and therapeutic considerations]. 1549 28

Cerebral excitability is normally distributed, and pubertal age is a distinguishing factor. The final developmental event in CNS comprising selective pruning of excitatory synapses coincides with puberty. With early puberty, excess excitation and synaptic density, we have photic susceptibility, paroxysmal EEGs, disturbed circadian rhythms, paroxysmal disorders treated with drugs lowering excitation. Manic-depressive psychosis accords with this. Migraine with paroxysmal EEG, photophobia, hemianopsia, scintillating scotomas, excess excitation in the visual system, benefits from lowering excitation. With late puberty, attenuated CNS, we have disorders in need of raising excitation to avoid breakdown of circuitry, insufficient fill-in mechanism, silent spots, subjectively experienced only--objectively verifiable psychosis: i.e., schizophrenia treated with convulsant neuroleptics. By affecting pubertal age, we affect the distribution of excitation and of post-pubertal brain disorders in accordance with their level of excitation. Excitation is equally important in chronic disorders: l'dopa adversity in Parkinsonism could be due to further lowering of excitation in patients with a deficiency, a schizophrenia-like psychosis develops. Given unavoidable adversity of anti-psychotics, and a marked rise in suicide in schizophrenic and manic-depressive since their introduction, we want to prevent the occurrence of disorders at the extremes, whether very early or late puberty. DHA normalises excitability at all levels of excitation. An adequate daily intake of DHA, before puberty as well as after, might probably reduce or eliminate a development of psychopathology. Lithium is a robust neurotropic agent, and lithiation of the drinking water could be a way of reducing suicide, homicide, violent behaviour, and drug abuse.
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PMID:A "new-old" way of thinking about brain disorder, cerebral excitability--the fundamental property of nervous tissue. 1553 32

The fact that so many varied medications reportedly affect taste and smell is a testament to the complexity of the gustatory and olfactory systems. The reception, transduction, propagation, and perception of a chemical tastant or odorant requires the effective operation of numerous mechanisms--all of which may be susceptible in one way or another to a prescribed medication. Just as a diuretic may block the apical ion channels on a taste bud, or an antifungal can inhibit cytochrome p450-dependent enzymes at the level of the receptors, a chemotherapeutic agent can destroy mitosis in a replicating receptor cell and a steroid can lead to candidal overgrowth on the tongue surface. Medications not only have a perceivable taste themselves at times, but they can alter the mechanisms responsible for the ultimate perception of tastes and smells--either by direct or secondary means. It should be emphasized, as noted earlier in this article, that while many medications are to blame for the impairment or distortion of the gustatory or olfactory systems, it is not uncommon that the underlying medical problem for which they are prescribed is actually the culprit. Examples include epilepsy, migraines, hypothyroidism, schizophrenia, infections, and cancer. In fact, simple partial seizures emanating from regions of the brain such as the amygdala, hippocampus, parietal operculum, and rolandic operculum can lead to the chemosensory sensations that are most commonly considered unpleasant, such as "rotten apples," "cigarette," "peculiar," or "vomitus". While removing or changing an offending medication can reverse the effects on smell or taste perception, it is important to remember that lasting impairment may occur. This is vital for a physician to recognize prior to prescribing a medication. It is also necessary to report this to patients who may be devastated by chemosensory alterations after starting a new medication (eg, pastry chef, perfumist, wine specialist, plumber). Among the "risks" in a risks/benefits discussion with a patient regarding the use of a new medication, alterations in olfaction and taste appear to play an increasingly recognized role.
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PMID:Effects of drugs on olfaction and taste. 1556 12

Since the cloning of the histamine H(3) receptor cDNA in 1999 by Lovenberg and co-workers, this histamine receptor has gained the interest of many pharmaceutical companies as a potential drug target for the treatment of various important disorders, including obesity, attention-deficit hyperactivity disorder, Alzheimer's disease, schizophrenia, as well as for myocardial ischaemia, migraine and inflammatory diseases. Here, we discuss relevant information on this target protein and describe the development of various H(3) receptor agonists and antagonists, and their effects in preclinical animal models.
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PMID:The histamine H3 receptor: from gene cloning to H3 receptor drugs. 1566 57

Celiac disease (CD) long has been associated with neurologic and psychiatric disorders including cerebellar ataxia, peripheral neuropathy, epilepsy, dementia, and depression. Earlier reports mainly have documented the involvement of the nervous system as a complication of prediagnosed CD. However, more recent studies have emphasized that a wider spectrum of neurologic syndromes may be the presenting extraintestinal manifestation of gluten sensitivity with or without intestinal pathology. These include migraine, encephalopathy, chorea, brain stem dysfunction, myelopathy, mononeuritis multiplex, Guillain-Barre-like syndrome, and neuropathy with positive antiganglioside antibodies. The association between most neurologic syndromes described and gluten sensitivity remains to be confirmed by larger epidemiologic studies. It further has been suggested that gluten sensitivity (as evidenced by high antigliadin antibodies) is a common cause of neurologic syndromes (notably cerebellar ataxia) of otherwise unknown cause. Additional studies showed high prevalence of gluten sensitivity in genetic neurodegenerative disorders such as hereditary spinocerebellar ataxia and Huntington's disease. It remains unclear whether gluten sensitivity contributes to the pathogenesis of these disorders or whether it represents an epiphenomenon. Studies of gluten-free diet in patients with gluten sensitivity and neurologic syndromes have shown variable results. Diet trials also have been inconclusive in autism and schizophrenia, 2 diseases in which sensitivity to dietary gluten has been implicated. Further studies clearly are needed to assess the efficacy of gluten-free diet and to address the underlying mechanisms of nervous system pathology in gluten sensitivity.
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PMID:Neurologic presentation of celiac disease. 1582 33

Antiepileptic drugs (AEDs) affect various neurotransmitters (i.e. GABA, glutamate), receptors (i.e. GABAergic, glutamatergic), and ion channels (i.e. for sodium or calcium) which is responsible for their anticonvulsant activity. However, this broad spectrum of action may be also utilized in other pathological conditions. For example, both conventional and newer AEDs may be used in patients suffering from neuropathic pain, migraine, essential tremor, spasticity, restless legs syndrome and a number of psychiatric disorders (f.e. bipolar disease or schizophrenia). Also, isolated data point to their potential use in Parkinson's or Alzheimer's disease. There is experimental background indicating a potent neuroprotective efficacy of AEDs in numerous models of brain ischemia. However, the clinical data are very limited and this problem requires careful assessment.
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PMID:Non-epilepsy uses of antiepilepsy drugs. 1653 24

Headaches are commonly associated with various psychiatric disorders. The comorbidity of migraine and psychiatric disorders has been well documented. Here we present a case of schizophrenia with comorbid headache treated with clozapine. The patient's headache fulfilled the diagnostic criteria for cluster headache (CH). To our knowledge this is the first report of CH responding to clozapine therapy. The relationship of headache and psychiatric disorders is a matter of debate and there has been very little research on the aspect of causality or direction of causation. The response of both the conditions to a serotonin-dopamine antagonist such as clozapine might be important in giving newer insights into the pathogenesis of these disorders. It also has the clinical implication of being useful in patients with dual diagnosis.
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PMID:Clozapine-responsive cluster headache. 1680 70

The 5-HT(2C) receptor subtype has been implicated in a wide variety of conditions including obesity, anxiety, depression, obsessive compulsive disorder, schizophrenia, migraine and erectile dysfunction and as a consequence has received considerable attention as a target for drug discovery. Here we review the pharmacological, pharmacokinetic and toxicological profile of WAY-163909 {(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole}, a novel 5-HT(2C) receptor selective agonist. Consistent with a potential therapeutic utility in obesity, schizophrenia and depression WAY-163909 was found to have robust dose-dependent effects in animal models of obesity, psychotic-like behavior or depression.
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PMID:Pharmacological profile of the 5-HT(2C) receptor agonist WAY-163909; therapeutic potential in multiple indications. 1722 85

Since the first mitochondrial dysfunction was described in the 1960s, the medicine has advanced in its understanding the role mitochondria play in health, disease, and aging. A wide range of seemingly unrelated disorders, such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis, have underlying pathophysiological mechanisms in common, namely reactive oxygen species (ROS) production, the accumulation of mitochondrial DNA (mtDNA) damage, resulting in mitochondrial dysfunction. Antioxidant therapies hold promise for improving mitochondrial performance. Physicians seeking systematic treatments for their patients might consider testing urinary organic acids to determine how best to treat them. If in the next 50 years advances in mitochondrial treatments match the immense increase in knowledge about mitochondrial function that has occurred in the last 50 years, mitochondrial diseases and dysfunction will largely be a medical triumph.
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PMID:Mitochondrial dysfunction and molecular pathways of disease. 1723 70

The cloning of the histamine H(3) receptor (H(3)R) cDNA in 1999 by Lovenberg et al. [10] allowed detailed studies of its molecular aspects and indicated that the H(3)R can activate several signal transduction pathways including G(i/o)-dependent inhibition of adenylyl cyclase, activation of phospholipase A(2), Akt and the mitogen activated kinase as well as the inhibition of the Na(+)/H(+) exchanger and inhibition of K(+)-induced Ca(2+) mobilization. Moreover, cloning of the H(3)R has led to the discovery several H(3)R isoforms generated through alternative splicing of the H(3)R mRNA. The H(3)R has gained the interest of many pharmaceutical companies as a potential drug target for the treatment of various important disorders like obesity, myocardial ischemia, migraine, inflammatory diseases and several CNS disorders like Alzheimer's disease, attention-deficit hyperactivity disorder and schizophrenia. In this paper, we review various molecular aspects of the hH(3)R including its signal transduction, dimerization and the occurrence of different H(3)R isoforms.
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PMID:Molecular aspects of the histamine H3 receptor. 1727 12


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