Central nervous system disorders schizophrenia

Histamine produces its pharmacological actions by three subtypes of receptors the postsynaptic Hi and H2 receptors and the presynaptic H3 receptor. The H3 receptor is mainly located in the central nervous system (CNS), where it acts as an inhibitory autoreceptor in the central histaminergic neuronal pathways [176]. A number of therapeutic applications have been proposed for selective H3 receptor antagonists, including several CNS disorders such as Alzheimer s disease. Attention Deficit Hyperactivity Disorder, Schizophrenia, or for enhancing memory or obesity control. 

Schizophrenia is a chronic, complex psychiatric disorder affecting approximately 1% of the population worldwide. The chronic nature of the illness, in addition to the early age of onset, results in direct and indirect health care expenditures in the U.S., which amount to approximately 30 to 64 billion dollars per year [4]. It is perhaps the most devastating of psychiatric disorders, with approximately 10% of patients committing suicide. The dopamine hypothesis of schizophrenia postulates that overactivity at dopaminergic synapses in the central nervous system (CNS), particularly the mesolimbic system, causes the psychotic symptoms (hallucinations and delusions) of schizophrenia. Roth and Meltzer [5] have provided a review of the literature and have concluded a role for serotonin as well in the pathophysiology and treatment of schizophrenia. The basic premise of their work stems from the known interaction between the serotonergic and dopaminergic systems. 

In this rapidly evolving field, the detection of PDE enzymes in the central nervous system (CNS) has stimulated interest in exploring potential applications of PDE inhibitors for treating CNS disorders such as Alzheimer s disease and other cognitive malfunctions, depression, anxiety, and schizophrenia. This review will focus on these therapeutic opportunities as well as new developments in the medicinal chemistry and biology associated with selected members of the PDE family, in particular PDEs 2, 4, 9, and 10. There have been a number of other reviews in this field in the past year that have covered selected individual PDE enzymes and potential pharmacologic applications of PDE inhibitors in CNS disorders [3,7,8]. 

As with research on drugs for the treatment of disease, an understanding of the mechanism by which mind-altering drugs operate is fundamental to the development of new chemicals to treat mental disorders, such as Parkinson s disease, schizophrenia, and depression. Scientists now understand that many abnormal mental conditions are the result ofbiochemical imbalances— an excess or deficiency of essential chemicals in the central nervous system—that can be ameliorated or cured by treatment with natural or synthetic drugs. 

In the central nervous system, there are close associations between NT and dopamine systems, and NT may be involved in clinical disorders involving dopamine pathways such as schizophrenia, Parkinson s disease, and drug abuse. Consistent with this, it has been shown that central administration of NT produces effects in rodents similar to those produced by antipsychotic drugs. 

Chlorpromazine Blockade of D2 receptors >> 5 2 receptors .-Receptor blockade (fluphenazine least) muscarinic (M)-receptor blockade (especially chlorpromazine and thioridazine) Hx-receptor blockade (chlorpromazine, thiothixene) t central nervous system (CNS) depression (sedation) t decreased seizure threshold t QT prolongation (thioridazine) Psychiatric schizophrenia (alleviate positive symptoms), bipolar disorder (manic phase) nonpsychiatric antiemesis, preoperative sedation (promethazine) pruritus Oral and parenteral forms, long half-lives with metabolism-dependent elimination Toxicity Extensions of effects on a - and M- receptors blockade of dopamine receptors may result in akathisia, dystonia, parkinsonian symptoms, tardivedyskinesia, and hyperprolactinemia... 

The co-3 fatty acids have numerous important functions, especially in the brain. Accordingly, a deficiency of DHA and EPA may cause dysfunction of the central nervous system and probably also the retina, thereby resulting in impaired vision. In addition, there is a variety of neurological and psychiatric disorders that have been associated with decreased levels of especially DHA and AA, such as, for example, schizophrenia and depression [3], post-traumatic stress syndrome, autism and attention deficit hyperactivity disorder. Since no primary inherited defect of essential fatty acid interconversion has yet been described, no specific explanations for the essential fatty acid concentration changes are readily available. 

Central nervous system. Depression and psychosis can occur during the first few days of high dose administration, especially in those with a history of mental disorder. Other effects include euphoria, insomnia, and aggravation of schizophrenia and epilepsy. Long-term treatment may result in raised intracranial pressure with papilloedema, especially in children. 

It was named Dopamine because it was a monoamine, and its synthetic precursor was 3,4-dihydroxyphenylalanine (L-DOPA). He was awarded Nobel Prize in 2000 along with Eric Kandel and Paul Greengard in Medicine for showing that dopamine is not just a precursor of noradrenaline and adrenaline, but also neurotransmitter as well. DO is a type of neurotransmitter naturally produced in by the human body. It is also a neurohormone released by the hypothalamus. It is a chemical messenger that is similar to adrenaline and affects the brain processes that control movement, emotional response, and the capacity to feel pleasure and pain. It is vital for performing balanced and controlled movements [172,173], In the extra-cellular fluid of the central nervous system, the basal DO concentration is very low (0.01-1 pM). Abnormal levels of DO have been linked with Parkinson s disease, Tourette s syndrome, Schizophrenia, attention deficit hyperactive disorder and generation of pituitary tumours [174-176],... 

Dopamine is a major catecholamine neurotransmitter in the central nervous system that has been implicated in the regulation of locomotor activity, emotion, cognition, and behavior reward and in neuroendocrine regulation [39]. Clinically, dopaminergic drugs (e.g., risperidone) that block or activate dopamine receptors are used to treat neurodegenerative, neuropsychiatric, and neurode-velopmental conditions such as Parkinson s, schizophrenia, bipolar disorder, and autism [40],... 

Berberine seems to have antidepressant and neuroprotective effects in several neurodegenerative and neuropsychiatric disorders. It has been reported to modulate neurotransmitters and their receptor systems in the brain. Moreover, some works indicate a beneficial effect of berberine in the treatment of central nervous system-related disorders including Alzheimer s disease, cerebral ischemia, schizophrenia, anxiety, and mental depression [68-71]. Supporting the observed effect of berberine on the central nervous system, Wang et al. showed that berberine can cross the blood-brain barrier and could be transported into the neurons in a concentration- and time-dependent manner [72]. 

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