quetiapine-fumarate and Neurodegenerative-Diseases

This manuscript reviews the preclinical in vitro, ex vivo, and nonhuman in vivo effects of psychopharmacological agents in clinical use on cell physiology with a view toward identifying agents with neuroprotective properties in neurodegenerative disease. These agents are routinely used in the symptomatic treatment of neurodegenerative disease. Each agent is reviewed in terms of its effects on pathogenic proteins, proteasomal function, mitochondrial viability, mitochondrial function and metabolism, mitochondrial permeability transition pore development, cellular viability, and apoptosis. Effects on the metabolism of the neurodegenerative disease pathogenic proteins alpha-synuclein, beta-amyloid, and tau, including tau phosphorylation, are particularly addressed, with application to Alzheimer's and Parkinson's diseases. Limitations of the current data are detailed and predictive criteria for translational clinical neuroprotection are proposed and discussed. Drugs that warrant further study for neuroprotection in neurodegenerative disease include pramipexole, thioridazine, risperidone, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, fluoxetine, buspirone, clonazepam, diphenhydramine, and melatonin. Those with multiple neuroprotective mechanisms include pramipexole, thioridazine, olanzapine, quetiapine, lithium, valproate, desipramine, maprotiline, clonazepam, and melatonin. Those best viewed circumspectly in neurodegenerative disease until clinical disease course outcomes data become available, include several antipsychotics, lithium, oxcarbazepine, valproate, several tricyclic antidepressants, certain SSRIs, diazepam, and possibly diphenhydramine. A search for clinical studies of neuroprotection revealed only a single study demonstrating putatively positive results for ropinirole. An agenda for research on potentially neuroprotective agent is provided.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Antipsychotic Agents; Benzodiazepines; Benzothiazoles; Brain; Clonazepam; Desipramine; Dibenzothiazepines; Dopamine Agonists; Humans; Lithium Carbonate; Maprotiline; Melatonin; Neurodegenerative Diseases; Neuroprotective Agents; Olanzapine; Parkinson Disease; Pramipexole; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Valproic Acid

Quetiapine combined with sodium valproate is an effective and more suitable drug treatment for Alzheimer's disease. At present, there are relatively few studies on the combined action mechanism of these two drugs. This study has certain practical value. Alzheimer's disease is a multifaceted, highly genetically heterogeneous neurodegenerative disease. The main clinical manifestations are memory loss, abnormal mental behavior, and loss of various cognitive functions. In order to improve the symptoms of patients with Alzheimer's disease, especially those with mental symptoms, this article combines quetiapine and sodium valproate, two commonly used drugs for the treatment of mental illnesses, and applies them to different levels of Alzheimer's and observes the results of the combination's curative effect. This article introduces Alzheimer's disease and its potential mental behaviors in the method section, and it also introduces the mechanism of action of quetiapine and sodium valproate. For the algorithm, this paper introduces a data mining algorithm to understand the effect of drug efficacy. In the experimental part, firstly, it introduces the experimental objects, the proportion of medicines, and the statistical methods. Secondly, this article covers adverse reactions, inflammatory factors and vascular endothelial indicators, Alzheimer's disease performance, MOAS score, treatment effect evaluation, and satisfaction surveys. It can be seen from the experiment that, in mental behavior, the experimental group decreased from 8.2 before treatment to 0.5, and the control group decreased from 7.1 before treatment to 2.6. It can be seen that the scores of the experimental group changed after receiving the treatment of quetiapine combined with sodium valproate.

Topics: Alzheimer Disease; Antipsychotic Agents; Behavioral Symptoms; Dibenzothiazepines; Humans; Neurodegenerative Diseases; Quetiapine Fumarate; Valproic Acid

Topics: Clozapine; Humans; Neurodegenerative Diseases; Parkinson Disease; Psychotic Disorders; Quetiapine Fumarate; United States

Reports on prenatal exposure to some of the first generation antipsychotic drugs like, haloperidol, their effects on fetal neurotoxicity and functional impairments in the offspring, are well documented. But studies on in utero exposure to second generation antipsychotics, especially quetiapine, and its effects on fetal neurotoxicity, apoptotic neurodegeneration, postnatal developmental delay and neurobehavioral consequences are lacking. Therefore, the present study was undertaken to evaluate the effect of prenatal administration to equivalent therapeutic doses of quetiapine on neuro-architectural abnormalities, neurohistopathological changes, apoptotic neurodegeneration in fetal hippocampus, and postnatal development and growth as well as its long-lasting imprint on cognitive impairment in young-adult offspring. Pregnant Wistar rats (n=24) were exposed to selected doses (55 mg, 80 mg and 100mg/kg) of quetiapine, equivalent to human therapeutic doses, from gestation day 6 to 21 orally with control subjects. Half of the pregnant subjects of each group were sacrificed at gestation day 21 for histopathological, confocal and electron microscopic studies and rest of the dams were allowed to deliver naturally. Their pups were reared postnatally up to 10 weeks of age for neurobehavioral observations. In quetiapine treated groups, there was significant alterations in total and differential thickness of three typical layers of hippocampus associated with neuronal cells deficit and enhanced apoptotic neurodegeneration in the CA1 area of fetal hippocampus. Prenatally drug treated rat offspring displayed post-natal developmental delay till postnatal day 70, and these young-adult rats displayed cognitive impairment in Morris water maze and passive avoidance regimes as long-lasting impact of the drug. Therefore, quetiapine should be used with cautions considering its developmental neurotoxicological and neurobehavioral potential in animal model, rat.

Topics: Analysis of Variance; Animals; Antipsychotic Agents; Apoptosis; Avoidance Learning; Cognition Disorders; Dose-Response Relationship, Drug; Female; Hippocampus; Male; Maze Learning; Microscopy, Electron; Neurodegenerative Diseases; Pregnancy; Prenatal Exposure Delayed Effects; Quetiapine Fumarate; Rats; Rats, Wistar

Quetiapine, a new atypical antipsychotic drug, has beneficial effects on cognitive impairment and neuropathological changes in treating chronic neurodegenerative diseases. Our previous studies have demonstrated that quetiapine may have neuroprotective properties. In the present study, we investigated the effects of a 2-week pre-administration of quetiapine (10 mg/kg/day, i.p.) on spatial memory impairment and hippocampal neurodegeneration induced by 60-minute bilateral common carotid artery occlusion (CCAO). Following a 7-day recovery phase from CCAO, the spatial memory of the mice was tested using a modified water maze test. After the behavioural test, the mice were sacrificed and brain sections were stained with NeuN (a neuron-specific soluble nuclear antigen), cresyl violet (Nissl), and Fluoro-Jade B. CCAO significantly induced spatial memory impairment and caused neurodegeneration in the hilus of hippocampus, while quetiapine significantly attenuated these changes. This is the first study showing that quetiapine significantly attenuates CCAO-induced spatial memory impairment and this improvement parallels the alleviative effects of quetiapine on CCAO-induced neurodegeneration in the hilus of hippocampus. The results suggest that quetiapine may have defending effects on the impairments induced by cerebral ischemia, which enhances our understanding about the mechanisms of quetiapine.

Topics: Animals; Carotid Arteries; Carotid Artery Diseases; Dibenzothiazepines; Hippocampus; Male; Maze Learning; Memory Disorders; Mice; Mice, Inbred ICR; Neurodegenerative Diseases; Quetiapine Fumarate; Staining and Labeling