Welcome to Raystarbio!Focus On Forefront Bioactive Compounds.
Find Your Distributors

Select Your Country or Region

$ USD

You are here:Home-Research Areas-Neurological Disease-Schizophrenia

Request The Product List ofSchizophrenia Schizophrenia

    Schizophrenia is a chronic, debilitating mental disorder affecting 1-2% of the global population. Symptoms are split into two types; 'positive' symptoms, including delusions and hallucinations, and 'negative' symptoms, including anhedonia and lack of motivation. Studies suggest that genetics, early environment, neurobiology, psychological and social processes are important contributory factors; some recreational and prescription drugs appear to cause or worsen symptoms. Several neurobiological alterations in brain structure, physiology and neurochemistry have been documented, along with an ever-increasing list of susceptibility genes.



    Pathogenesis of Schizophrenia

    Schizophrenia has been associated with the dysregulation of many neurotransmitter systems. Excessive dopamine is the oldest and most widely accepted theory of the pathophysiology of schizophrenia and stems from identification of dopamine D2 receptor blockade as the mechanism of action of antipsychotics. Dopamine D2 binding sites are increased in schizophrenic brains, whilst there are prefrontal D1 deficits, which contributes to cognitive impairment. The current understanding suggests that a hyperactive mesolimbic and a hypoactive mesocortical dopamine system underlie the 'positive' and 'negative' symptoms respectively that are seen in schizophrenia.

    In addition to dopamine, serotonin, glutamate, GABA and acetylcholine dysregulation have also been implicated in the pathogenesis of schizophrenia. Glutamatergic signaling is attenuated in schizophrenia and is characterized by a loss of NMDA receptor-mediated excitatory neurotransmission. GABA levels are also attenuated due to downregulation of GABA transporter (GAT) gene expression. There is a concordant upregulation of GABAA receptors, which may contribute to the alterations in neural synchrony and consequently working memory impairment.

    Over the last twenty years there has been an explosion in the knowledge of the neurobiology of schizophrenia, yet a precise understanding of its etiology and pathogenesis has remained elusive.


    CNS Changes in Schizophrenia

    Numerous neuroanatomical alterations are seen in the brains of schizophrenic patients. At the gross level, overall brain volume and grey matter volume is reduced in schizophrenic brains and ventricular volume (particularly the third and fourth ventricles) is increased. These changes in brain structure are seen early after, and sometimes prior to, onset of symptoms and can be progressive. White matter volume is also decreased in brains of schizophrenic patients and is consistent with the cognitive deficits seen in this disease. Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis is prevalent in schizophrenics and this has been linked to an increase in the severity of the above structural changes. The structural changes seen are subtle and there is evidence to suggest that schizophrenia arises from minor abnormalities in neurodevelopment, such as disordered cortical neuron migration.


    Susceptibility Genes for Schizophrenia

    Schizophrenia genetics are complex and several genomic loci are likely to harbor genes conferring risk for this disease.

  ~DISC1 has emerged as a strong candidate for a susceptibility gene. The molecular and cellular interactions of DISC1 are critical for normal neuronal development and in the adult are implicated in neuronal signal transduction and plasticity. DISC1 polymorphisms are associated with altered hippocampal function and identification of this gene supports the notion that schizophrenia is a disorder of cortical development.

  ~Neuregulin 1 signals via ErbB receptors to regulate NMDA receptor density and has been implicated in neuronal differentiation and migration. In schizophrenia, neuregulin 1 signaling is enhanced, leading to NMDA receptor suppression, which is consistent with the glutamate hypofunction hypothesis.

  ~Dysbindin has been reported to influence glutamate neurotransmission and reduced levels of this protein have been found in schizophrenic brains.

  ~D-amino acid oxidase activator (DAOA) has also been associated with schizophrenia. DAOA activates D-amino acid oxidase (DAO), which is a coagonist at NMDA receptors.

  ~Catechol-O-methyltransferase (COMT) participates in dopamine clearance from synapses and has been implicated in regulation of neurotransmission related to schizophrenia. A functional polymorphism in the COMT gene alters activity of this enzyme and homozygosity correlates to increased dopamine levels in critical central synapses.


   Pharmacological Intervention

   First line pharmacological intervention of schizophrenia currently employs atypical antipsychotics such as clozapine and amisulpride. Typical antipsychotics, such as the dopamine receptor antagonists chlorpromazine and haloperidol, have been available since the 1950s but are less commonly used now due to their adverse side effects. Antipsychotics are effective at reducing the 'positive' symptoms of this disease, but often have very little efficacy in reducing the 'negative' symptoms.

Cat. No. Product Name CAS No. Information
GY10591

LY2140023

635318-55-7

LY2140023 is the methionine amide prodrug of the mGluR2/3 agonist LY-404039 with the potential oral treatment of schizophrenia.

GY04325

PF-2545920

898562-94-2

A potent and selective PDE10A inhibitor with IC50 of 0.37 nM; displays >1,000-fold selectivity over the PDEs; antagonizes apomorphine-induced climbing in mice, inhibits conditioned avoidance responding in both rats and mice, and blocks NMDA antagonist-induced deficits in prepulse inhibition of acoustic startle response in rats; dose-dependently increases c-Fos immunopositive nuclei in all regions of neostriatum in the DRd1a-tdTomato mice; improves cortico-basal ganglia function in huntington's disease models; orally bioavailable.

GY03885

NE-100

149409-57-4

A potent, selective, and orally active sigma-1 receptor antagonist with Ki of 1.03 nM; dispalys 205-fold selectivity over sigma-2, 1,000-fold selectivity over D1, D2, PCP, α1, 5-HT1A and 5-HT2 receptors; shows antipsychotic activity in vivo.

GY07041

TAK-915

1476727-50-0

TAK-915 (TAK915) is a highly potent, selective, brain-penetrating and orally active phosphodiesterase 2A (PDE2A) inhibitor with IC50 of 0.61 nM; dispalys 4100-fold selectivity over PDE1A, and >20,000-fold over other PDE isoforms; robustly increased cGMP levels in the rat brain, attenuates MK-801-induced episodic memory deficits in rats.

GY06794

LY500307

533884-09-2

LY500307 (LY-500307, Erteberel, SERBA-1) is a potent, selective Estrogen Receptor β (ERβ) agonist with Ki/EC50 of 0.19/0.66 nM, 12-fold higher affinity than ERα and exhibits 32-fold more functional potency; reduces proliferation and induces apoptosis in GBM cells, enhances ERβ signaling and expression, modulates the expression of genes involved in cell cycle, cell death, survival, and DNA damage response; also sensitizes GBM cells to chemotherapeutic agents, reduces GBM progression in an orthotopic model .

GY02034

PF-2545920 hydrochloride

A potent and selective PDE10A inhibitor with IC50 of 0.37 nM; displays >1,000-fold selectivity over the PDEs; antagonizes apomorphine-induced climbing in mice, inhibits conditioned avoidance responding in both rats and mice, and blocks NMDA antagonist-induced deficits in prepulse inhibition of acoustic startle response in rats; dose-dependently increases c-Fos immunopositive nuclei in all regions of neostriatum in the DRd1a-tdTomato mice; improves cortico-basal ganglia function in huntington's disease models; orally bioavailable.

GY04042

TAK063

1238697-26-1

TAK-063 (Balipodect) is a highly potent, selective, orally active PDE10A inhibitor with IC50 of 0.3 nM, displays >15,000-fold selectivity over other PDE subtypes; increases cAMP and cGMP levels in the rodent striatum and upregulates phosphorylation levels of key substrates of cAMP- and cGMP-dependent protein kinases, strongly suppresses MK-801-induced hyperlocomotion in rodents (0.3 and 1 mg/kg p.o), improves cognitive functions associated with schizophrenia in rodent models,

GY05358

Basmisanil

1159600-41-5

A novel selective negative allosteric modulator of the GABAA receptor α5-subtype, which is under development for the treatment of cognitive impairment associated with Down syndrome.

GY05333

BMS-933043

1221973-93-8

BMS-933043 is a novel highly selective, potent α7 nAChR partial agonist with binding Ki of 3.3 and 8.1 nM for rat and human α7, respectively; displays high selectivity against other nAChR subtypes (>100-fold) and 5-HT3A receptor (>300-fold); demonstrates in vivo activity in a preclinical model of cognitive impairment, mouse novel object recognition.

GY05331

AMG-579

1227067-61-9

AMG-579 is a potent, selective, CNS penetrant, orally bioavailable PDE10A inhibitor with IC50 of 0.1 nM; displays high selectivity with IC50 > 30 uM against all other PDE isoforms; demonstrates excellent target occupancy efficacy in PCP-LMA behavioral model.

Request The Product List

* Indicates a Required FieldYour information is safe with us.

  • *Product List:
  • *Applicant name:
  • *Email address:
  • *Organization name:
  • *Country:
  • Additional Information:
© Copyright 2020 RayStarBio. All Rights Reserved. Products are only for research use