Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Akathisia and tardive dyskinesia are thought to be different entities, while tardive akathisia is considered a variant of akathisia. In the case presented, tardive akathisia first appeared when phenothiazine medication was stopped and then, following a cerebrovascular accident, tardive akathisia disappeared with the emergence of tardive dyskinesia. This case suggests the possibility of a relationship between these 2 disorders.
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PMID:[Tardive akathisia and tardive dyskinesia]. 167 23

Involuntary mouthing movements indistinguishable from neuroleptic-induced tardive dyskinesia followed stroke in a woman whose computed tomographic (CT) scan showed bilateral thalamo-capsular infarction.
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PMID:Oral dyskinesias associated with bilateral thalamo-capsular infarction. 231 5

Affective illness is common, frequently debilitating, and sometimes life-threatening in the elderly. Considerations pertaining to treatment with heterocyclic drugs, MAOIs, lithium, psychostimulants and thyroid hormone, as well as ECT, have been reviewed. Amitriptyline and imipramine cause significant orthostatic hypotension and probably should be avoided in the elderly. In addition, amitriptyline is extremely anticholinergic. Amoxapine is essentially a neuroleptic sequelae, including tardive dyskinesia. If a patient has had a prior positive response or has a relative who had a good outcome from a particular drug, it may be best to begin treatment with that drug. Initial choice of antidepressant can be based largely on the clinical picture. For example, if a depressed patient is sleeping much more than usual, try a potentially activating agent like desipramine or protriptyline. if, on the other hand, the patient is unable to sleep, a more sedating agent like nortriptyline, maprotiline, trimipramine, or trazodone should be tried. Risks and side effects of these drugs, as well as their use in cardiac patients, have been reviewed in detail. Many clinicians avoid MAOIs in elderly patients because of fear of adverse reactions. This fear is largely unfounded. Precautions, side effects, and specific recommendations have been outlined. Using lithium in the elderly requires special precautions because of decreased GFR and potential interactions with concomitantly used drugs. This paper has discussed possible side effects and toxicity. The usage of psychostimulants, such as methylphenidate and amphetamine, to treat medically ill depressed patients is reviewed. These agents are also sometimes useful in demented individuals or in patients with abulic frontal lobe syndromes. Poststroke depressions are common, and recent evidence indicates that they can be adequately treated. Stroke patients have many difficulties dealing with rehabilitation and should not be forced to suffer concomitant depression when we have the tools at hand to effectively treat such symptoms. Recent data on the potentiation of antidepressant effects by lithium or T3 indicate that they may be useful adjuvants in some tricyclic-resistant patients. Risks, side effects, and recent procedural advances in the use of ECT have been reviewed. Electroconvulsive therapy is both more effective and faster-acting than drugs in the treatment of depression. Many depressed elderly patients, especially those with psychotic symptoms, do not respond to drugs but improve with ECT.
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PMID:Treatment of affective illness in the elderly with drugs and electroconvulsive therapy. 269 55

BMY 14802 was identified as a potential antipsychotic drug in traditional model systems, and this identification was confirmed in modern behavioral and electrophysiological systems. The drug appears to be atypical as an antipsychotic in its lack of activity in models predictive of the potential to produce extrapyramidal side effects and tardive dyskinesia. Indeed, this suggestion is corroborated by clinical findings to date. The atypical profile of BMY 14802 extends to its neurochemical actions and appears to find its basis in regionally selective, indirect modulation of the dopamine system. Furthermore, BMY 14802 exhibits interactions with sigma binding sites in vitro and in vivo, a notion supported by data from neurophysiological, behavioral, and biochemical investigations. BMY 14802 also appears to be neuroprotective in some model systems and may have utility in the treatment of stroke (Boissard et al. 1991). BMY 14802 appears to interact with 5-HT1A receptors, but this interaction does not seem to contribute significantly to the potential antipsychotic actions of the drug. Moreover, the formation of active metabolites of BMY 14802 does not appear to occur in animals or humans to an extent of physiological or behavioral relevance. If clinically efficacious, BMY 14802 may treat the symptoms of schizophrenia by a mechanism novel for antipsychotic drugs: regionally selective, indirect modulation of dopaminergic systems by specific interaction at sigma sites.
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PMID:A role for sigma binding in the antipsychotic profile of BMY 14802? 823 11

A retrospective analysis of 812 patients admitted to the Ross Tilley Burn Centre between 1984 and 1992 resulted in 37 cases of burn injuries which were directly related to premorbid disabilities. The majority of these burns (83.8 per cent) occurred in the patient's home, most commonly as scald injuries in the bath tub, the shower, or following hot water spills. Nineteen patients were male, 17 were female. The median age was 58 years. Six patients had spinal cord disorders: four had traumatic cord damage, two had spina bifida. Six patients had seizure disorders. Five of these patients had been taking anti-seizure medications, but all had subtherapeutic blood levels on admission to hospital. Two patients had diabetes mellitus with peripheral neuropathies. Thirteen patients had four miscellaneous neurological disorders, including: tardive dyskinesia (two), CVA (four), Parkinson's disease (two), Alzheimer's disease (two), cerebral palsy (one), multiple sclerosis (one) and blindness (one). Three patients had a diagnosis of syncope. Two patients had emphysema, and four were morbidly obese. The average length of stay (LOS) for the disabled patients was 27.6 days for a median burn size of 10 per cent body surface area (BSA), compared to an average LOS for the general population of 25.7 days for a larger median burn size of 21 per cent BSA. The mortality rate was also much higher in the disabled population (22.2 per cent vs. 6.0 per cent). Most of these burn injuries were preventable. A series of burn prevention guidelines is presented, in an attempt to reduce the incidence of these burn injuries in disabled patients.
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PMID:Burns in the disabled. 850 62

Neurological disorders, such as stroke, trauma, tardive dyskinesia, Alzheimer's and Parkinson's diseases, may be partially attributed to excessive exposition of the nervous tissue to oxygen-derived radicals. A novel water-soluble alpha-tocopherol analogue, 2,3-dihydro-2,2,4,6,7-pentamethyl-3-(4-methylpiperazino) methyl-1-benzofuran-5-ol dihydrochloride (MDL), is a potent radical scavenger. Following subcutaneous administration to mice, MDL inhibited the lipid peroxidation induced in the 100-fold diluted brain homogenates, with an ID50 of 8 mg/kg. Rapid brain penetration, within 30-60 min postadministration, and even distribution into different brain areas were observed. MDL was also detected after oral administration. In brain homogenate undergoing lipid peroxidation, MDL prevented the consumption of an equal amount of alpha-tocopherol, while inhibiting the concomitant malondialdehyde formation. The radical scavenging capacity of MDL was superior to that of alpha-tocopherol, although the peak and half-peak potentials were not significantly different. However, MDL was much less lipophilic, the partition coefficient (log P) at the octanol/water interface being 1.91. Although it is yet unknown, whether the applied criteria sufficiently predict its usefulness, beneficial effects of MDL may be expected in the above mentioned disorders.
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PMID:Amphiphilic alpha-tocopherol analogues as inhibitors of brain lipid peroxidation. 886 17

The success of the low affinity use-dependent NMDA receptor antagonists to reach clinical trials can be readily attributed to their wider margins of safety and lack of neurotoxicity at higher doses. Several mechanistic differences distinguish the low affinity from the high affinity use-dependent antagonists: 1) Differential regional affinities for the various NMDA receptor subtypes; 2) The static receptor blockade due to the faster on/off rate receptor kinetics which limit, but do not totally prevent the amount of Ca+2 entry into the cell during glutamate-induced depolarization; and 3) Rapid egress of the compounds from the ion channel during recovery resulting in less membrane trapping between transmission pulses. Advanced clinical trials are in progress for the following indications: epilepsy, stroke, head trauma, tardive dyskinesia, pain plus Parkinson's, Huntington's and Alzheimer's diseases.
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PMID:Low affinity use-dependent NMDA receptor antagonists show promise for clinical development. 1102 83

The authors provide an extensive review of new data related to the role of glutamate in CNS disorders, describing new aspects in glutamate and glutamatergic receptors-NMDA receptors, NR2B-selective antagonists, non-NMDA ionotropic glutamate receptors, N-acetylaspartylglutamate, and glutamate and glycine transporters. New findings in animal models and in human diseases-stroke, traumatic brain injury, Alzheimer's, Parkinson's and Huntington's diseases, tardive dyskinesia, ALS, olivopontcerebellar degeneration, AIDS, allergic encephalomyelitis, epilepsy, anxiety, depression, schizophrenia, liver disease, aminoglycoside antibiotic-induced hearing loss, hemiplegia, chronic pain and drug tolerance and abuse-are presented. Finally, the authors cite the progress achieved in the development of agents that interact with the glutamatergic system: NMDA channel blockers, competitive NMDA receptor antagonists, NR2B-selective antagonists, glutamate release inhibitors, glycineB antagonists, AMPA and kainate receptor antagonists, AMPA receptor-positive modulators and agents that act by modifying endogenous kynurenic acid metabolism.
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PMID:Glutamate in CNS disorders as a target for drug development: an update. 1561 69

This paper reviews the main neurological complications of psychiatric drugs, in particular antipsychotics and antidepressants. Extrapyramidal syndromes include acute dystonia, parkinsonism, akathisia, tardive dyskinesia and tardive dystonia. Extrapyramidal symptoms (EPS) are less frequent with atypical than with conventional antipsychotics but remain common in clinical practice partly due to lack of screening by health professionals. Neuroleptic malignant syndrome (NMS) consists of severe muscle rigidity, pyrexia, change in conscious level and autonomic disturbance but partial forms also occur. NMS is particularly associated with the initiation and rapid increase in dose of high-potency antipsychotics but it has been reported with all the atypical antipsychotics and rarely with other drugs including antidepressants. Serotonin toxicity comprises altered mental state (agitation, excitement, confusion), neuromuscular hyperactivity (tremor, clonus, myoclonus, hyper-reflexia) and autonomic hyperactivity and occurs on a spectrum. Severe cases, termed serotonin syndrome, usually follow the co-prescription of drugs that increase serotonergic transmission by different pathways, for example a monoamine oxidase inhibitor (MAOI) and a selective serotonin reuptake inhibitor (SSRI). Most antipsychotics and antidepressants lower the seizure threshold and can cause seizures; the risk is greater with clozapine than with other atypical antipsychotics and greater with tricyclic antidepressants (TCAs) than with SSRIs. In randomised controlled trials in elderly patients with dementia atypical antipsychotics are associated with a higher risk of stroke and death than placebo. Cohort studies suggest that conventional drugs carry at least the same risk. Cessation of treatment with antipsychotics and antidepressants can lead to a wide range of discontinuation symptoms which include movement disorders and other neurological symptoms. Clinicians need to be familiar with strategies to reduce the risk of these adverse events and to manage them when they arise. Their occurrence needs to be balanced against the benefits of psychiatric drugs in terms of efficacy and improved quality of life in a range of disorders.
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PMID:Neurological complications of psychiatric drugs: clinical features and management. 1809 17

There is an increasing interest in nootropic drugs for the treatment of CNS disorders. Since the last meta-analysis of the clinical efficacy of piracetam, more information has accumulated. The primary objective of this systematic survey is to evaluate the clinical outcomes as well as the scientific literature relating to the pharmacology, pharmacokinetics/pharmacodynamics, mechanism of action, dosing, toxicology and adverse effects of marketed and investigational drugs. The major focus of the literature search was on articles demonstrating evidence-based clinical investigations during the past 10 years for the following therapeutic categories of CNS disorders: (i) cognition/memory; (ii) epilepsy and seizure; (iii) neurodegenerative diseases; (iv) stroke/ischaemia; and (v) stress and anxiety. In this article, piracetam-like compounds are divided into three subgroups based on their chemical structures, known efficacy and intended clinical uses. Subgroup 1 drugs include piracetam, oxiracetam, aniracetam, pramiracetam and phenylpiracetam, which have been used in humans and some of which are available as dietary supplements. Of these, oxiracetam and aniracetam are no longer in clinical use. Pramiracetam reportedly improved cognitive deficits associated with traumatic brain injuries. Although piracetam exhibited no long-term benefits for the treatment of mild cognitive impairments, recent studies demonstrated its neuroprotective effect when used during coronary bypass surgery. It was also effective in the treatment of cognitive disorders of cerebrovascular and traumatic origins; however, its overall effect on lowering depression and anxiety was higher than improving memory. As add-on therapy, it appears to benefit individuals with myoclonus epilepsy and tardive dyskinesia. Phenylpiracetam is more potent than piracetam and is used for a wider range of indications. In combination with a vasodilator drug, piracetam appeared to have an additive beneficial effect on various cognitive disabilities. Subgroup 2 drugs include levetiracetam, seletracetam and brivaracetam, which demonstrate antiepileptic activity, although their cognitive effects are unclear. Subgroup 3 includes piracetam derivatives with unknown clinical efficacies, and of these nefiracetam failed to improve cognition in post-stroke patients and rolipram is currently in clinical trials as an antidepressant. The remaining compounds of this subgroup are at various preclinical stages of research. The modes of action of piracetam and most of its derivatives remain an enigma. Differential effects on subtypes of glutamate receptors, but not the GABAergic actions, have been implicated. Piracetam seems to activate calcium influx into neuronal cells; however, this function is questionable in the light of findings that a persistent calcium inflow may have deleterious impact on neuronal cells. Although subgroup 2 compounds act via binding to another neuronal receptor (synaptic vesicle 2A), some of the subgroup 3 compounds, such as nefiracetam, are similar to those of subgroup 1. Based on calculations of the efficacy rates, our assessments indicate notable improvements in clinical outcomes with some of these agents.
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PMID:Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders. 2016 67


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