Parkinson histamine

Introduction : Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction and a diverse range of nonmotor symptoms. Functional relationships between the dopaminergic and histaminergic systems suggest that dual-action pharmaceuticals like AG-0029 (D2 /D3 agonist/H3 antagonist) could ameliorate both the motor and cognitive symptoms of PD. The current study aimed to demonstrate the interaction of AG-0029 with its intended targets in the mammalian brain using positron emission tomography (PET)...

A relationship appears to exist between dysfunction of brain histamine (HA) and various neuropsychiatric brain disorders. The possible involvement of brain HA in neuropathology has gained attention recently, and its role in many (patho)physiological brain functions including memory, cognition, and sleep-wake cycle paved the way for further research on the etiology of several brain disorders. Histamine H3 receptor (H3R) evidenced in the brains of rodents and humans remains of special interest, given its unique position as a pre- and postsynaptic receptor, controlling the synthesis and release of HA as well as different other neurotransmitters in different brain regions, respectively...

Parkinson disease (PD) is a neurodegenerative disorder of the motor activity of the brain, regulated by dopaminergic neurons of substantia nigra, resulting in an increased density of histaminergic fibers. This study was aimed to evaluate the effects of H1 antagonist's ebastine and levocetirizine in PD per se and in combination. Animals were divided into 9 groups ( n = 10). Group 1 received carboxymethyl cellulose CMC (1 mL/kg). Group II was treated with haloperidol (1 mg/kg) (diseased group). Group III was treated with levodopa/carbidopa (levo 20 mg/kg)...

Microglia, a category of glial cells in the central nervous system (CNS), have attracted much attention because of their important role in neuroinflammation. Many translational studies are currently ongoing to discover novel drugs targeting microglia for the treatment of various CNS disorders, such as Alzheimer's disease, Parkinson's disease (PD), and depression. Recent studies have shown that brain histamine, a neurotransmitter essential for the regulation of diverse brain functions, controls glial cells and neurons...

Memory, cognition, dementia, and neurodegeneration are complexly interlinked processes through various mechanistic pathways leading to a range of clinical outcomes. These are strongly associated with pathological conditions like Alzheimer's disease, Parkinson's disease, schizophrenia, stroke and are a growing concern for their timely diagnosis and management. Several cognition-enhancing interventions for management include non-pharmacological interventions like diet, exercise, and physical activity, while pharmacological interventions include medicinal agents, herbal agents, and nutritional supplements...

An increased concentration of histamine was found in the globus pallidus of parkinsonian patients. The role of this abnormality in the development of parkinsonism is unclear. We examined cataleptogenic activity of histamine injected into the globus pallidus (GP); also, the role of H2 receptors in histamine effect was evaluated. Given a possible role of the GP in integration and processing of stress signals, we tested the involvement of CRF1 receptors in the regulation of histamine effect. The experiments were conducted with male Wistar rats, catalepsy was assessed using bar test...

For several decades, interest in pyrrole and pyrrolopyrimidine derivatives increases owing to their biological importance, such as anti-tumor, anti-microbial, anti-inflammatory, anti-diabetic, anti-histaminic, anti-malarial, anti-Parkinson, antioxidant and anti-viral, specially recently against COVID-19. These tremendous biological features motivated scientists to discover more pyrrole and fused pyrrole derivatives, owing to the great importance of the pyrrole nucleus as a pharmacophore in many drugs, and motivated us to present this article, highlighting on the different synthetic pathways of pyrrole and its fused compounds specially pyrrolopyrimidine, as well as their medicinal value from 2017 till 2021...

BACKGROUND: Trazodone is prescribed off-label to treat insomnia, especially in older, not depressed adults. At low doses, it blocks histamine-1 (H1) receptors having a hypnotic effect. Unusual but potentially severe side effects of trazodone include suicidal behavior, excess sedation, QT prolongation, and priapism. Three case studies have been published in the last four decades describing trazodone-induced parkinsonism. CASE PRESENTATION: A 78-year-old Caucasian male with a past medical history of paroxysmal atrial fibrillation (on amiodarone), major depressive disorder, chronic obstructive pulmonary disease, hypothyroidism, and obstructive sleep apnea, was prescribed trazodone for his chronic insomnia...

BACKGROUND: Older patients affected with comorbidities often take a lot of potentially inappropriate drugs. This can cause side effects, hospitalization and even death. AIM: The aim of the present study was to assess dangerous drug interactions and potentially inappropriate drugs administered to a sample of ambulatory and home care patients affected with dementia. METHODS: 41 ambulatory outpatients and 53 home care patients affected with dementia were selected randomly between January 1st 2017 and December 31st 2019...

No abstract text is available yet for this article.

Monoamine oxidase (MAO) deficiency and imbalanced levels of brain monoamines have been associated with developmental delay, neuropsychiatric disorders and aggressive behavior. Animal models are valuable tools to gain mechanistic insight into outcomes associated with MAO deficiency. Here, we report a novel genetic model to study the effects of mao loss of function in zebrafish. Quantitative PCR, in situ hybridization and immunocytochemistry were used to study neurotransmitter systems and expression of relevant genes for brain development in zebrafish mao mutants...

Military personnel deployed in combat operations are highly prone to develop Parkinson's disease (PD) in later lives. PD largely involves dopaminergic pathways with hallmarks of increased alpha synuclein (ASNC), and phosphorylated tau (p-tau) in the cerebrospinal fluid (CSF) precipitating brain pathology. However, increased histaminergic nerve fibers in substantia nigra pars Compacta (SNpc), striatum (STr) and caudate putamen (CP) associated with upregulation of Histamine H3 receptors and downregulation of H4 receptors in human cases of PD is observed in postmortem cases...

Cassia obtusifolia L., of the Leguminosae family, is used as a diuretic, laxative, tonic, purgative, and natural remedy for treating headache, dizziness, constipation, tophobia, and lacrimation and for improving eyesight. It is commonly used in tea in Korea. Various anthraquinone derivatives make up its main chemical constituents: emodin, chrysophanol, physcion, obtusifolin, obtusin, au rantio-obtusin, chryso-obtusin, alaternin, questin, aloe-emodin, gluco-aurantio-obtusin, gluco-obtusifolin, naphthopyrone glycosides, toralactone-9-β-gentiobioside, toralactone gentiobioside, and cassiaside...

Histamine does not only modulate the immune response and inflammation, but also acts as a neurotransmitter in the mammalian brain. The histaminergic system plays a significant role in the maintenance of wakefulness, appetite regulation, cognition and arousal, which are severely affected in neuropsychiatric disorders. In this review, we first briefly describe the distribution of histaminergic neurons, histamine receptors and their intracellular pathways. Next, we comprehensively summarize recent experimental and clinical findings on the precise role of histaminergic system in neuropsychiatric disorders, including cell-type role and its circuit bases in narcolepsy, schizophrenia, Alzheimer's disease, Tourette's syndrome and Parkinson's disease...

In contrast to that of other monoamine neurotransmitters, the association of the histaminergic system with neuropsychiatric disorders is not well documented. In the last two decades, several clinical studies involved in the development of drugs targeting the histaminergic system have been reported. These include the H3R-antagonist/inverse agonist, pitolisant, used for the treatment of excessive sleepiness in narcolepsy, and the H1R antagonist, doxepin, used to alleviate symptoms of insomnia. The current review summarizes reports from animal models, including genetic and neuroimaging studies, as well as human brain samples and cerebrospinal fluid measurements from clinical trials, on the possible role of the histaminergic system in neuropsychiatric disorders...

OBJECTIVE: To investigate how common modifiable exposures, including dietary factors, select toxicants, and anti-inflammatory medications, may affect Parkinson's disease. METHODS: Using surveys, a case-control study was conducted at a medical center, comparing Parkinson's disease patients ( N   =  149) and healthy controls ( N   =  105). Subjects reported exposure to red meats, vegetables, alcohol, tobacco, anti-inflammatory medications, and pesticides...

Histamine is a biogenic amine playing a central role in allergy and peripheral inflammatory reactions and acts as a neurotransmitter and neuromodulator in the brain. In the adult, histamine is produced mainly by mast cells and hypothalamic neurons, which project their axons throughout the brain. Thus, histamine exerts a range of functions, including wakefulness control, learning and memory, neurogenesis, and regulation of glial activity. Histamine is also known to modulate innate immune responses induced by brain-resident microglia cells and peripheral circulating monocytes, and monocyte-derived cells (macrophages and dendritic cells)...

A major challenge in the field of the biogenic amine histamine is the search for new-generation histamine receptor specific drugs. Daniel Bovet and Sir James Black received their Nobel Prizes for Medicine for their work on histamine-1 receptor (H1 R) and H2 R antagonists to treat allergies and gastrointestinal disorders. The first H3 R-targeting drug to reach the market was approved for the treatment of the neurological disorder narcolepsy in 2018. The antagonists for the most recently identified histamine receptor, H4 R, are currently under clinical evaluation for their potential therapeutic effects on inflammatory diseases such as atopic dermatitis and pruritus...

The tuberomamillary nucleus (TMN) is located within the posterior part of the hypothalamus. The histamine neurons in it synthesize histamine by means of the key enzyme histidine decarboxylase (HDC) and from the TMN, innervate a large number of brain areas, such as the cerebral cortex, hippocampus, amygdala as well as the thalamus, hypothalamus, and basal ganglia. Brain histamine is reduced to an inactivated form, tele-methylhistamine (t-MeHA), by histamine N-methyltransferase (HMT). In total, there are four types of histamine receptors (H1-4 Rs) in the brain, all of which are G-protein coupled...

Adenosine A1 /A2A receptors (A1 R/A2A R) represent targets in nondopaminergic treatment of motor disorders such as Parkinson's disease (PD). As an innovative strategy, multitargeting ligands (MTLs) were developed to achieve comprehensive PD therapies simultaneously addressing comorbid symptoms such as sleep disruption. Recognizing the wake-promoting capacity of histamine H3 receptor (H3 R) antagonists in combination with the "caffeine-like effects" of A1 R/A2A R antagonists, we designed A1 R/A2A R/H3 R MTLs, where a piperidino-/pyrrolidino(propyloxy)phenyl H3 R pharmacophore was introduced with overlap into an adenosine antagonist arylindenopyrimidine core...