Schizophrenia
The main treatment difficulty within schizophrenia has to do with managing the negative and cognitive symptoms, which do not respond to the existing dopamine-based antipsychotics. Protheragen are developing novel therapies because of our leadership in the schizophrenia research field. As your reliable collaborator in schizophrenia drug development research, we offer unmatched research support.
Introduction to Schizophrenia
Schizophrenia develops as a combination of positive symptoms (hallucinations, delusions), negative symptoms, (avolition, affective flattening) and cognitive deficits (executive function impairment, impaired working memory). It is a chronic and severe neuropsychiatric disorder that develops in response to intricate gene and environmental interactions that disrupt neurodevelopmental processes and integrate faulty dopamine and glutamate neurotransmission as well as disrupt brain circuitry connectivity. The disorder usually manifests during late teenage years or early adulthood and is functionally debilitating.
Fig.1 Pathophysiology of schizophrenia-dopamine pathway. (Wani S N, et al., 2024)
Pathogenesis of Schizophrenia
The development of schizophrenia is associated with multiple genetic factors in combination with environmental insults that disturb neurodevelopment and result in aberrant synaptic pruning, GABAergic interneuron NMDAR hypofunction, and later cortical disinhibition. This causes disordered dopaminergic signaling and systems neurobiology with primary and secondary structural and functional changes in the frontal, temporal, and hippocampal regions, giving rise to the disorder's hallmark positive, negative, and cognitive symptoms.
Fig.2 Schematic of the hypothetical model of microglial activation and cognitive impairment in schizophrenia, and potential therapeutic agents. (Zhuo C, et al., 2023)
Therapeutic Development for Schizophrenia
| Drug Name | Mechanism of Action | Targets | NCT Number | Research Phase |
| Xanomeline and Trospium Chloride | Dual M1/M4 muscarinic receptor agonist (Xanomeline) with peripheral anticholinergic (Trospium) to improve tolerability | Muscarinic acetylcholine receptors M1/M4 | NCT06924255 | Phase III |
| Diroximel Fumarate (DRF) | Activates the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, modulating antioxidative and anti-inflammatory responses | Nrf2 transcription factor | NCT06957808 | Phase II |
| Brexpiprazole | Partial agonist at serotonin 5-HT1A and dopamine D2 receptors; antagonist at 5-HT2A and noradrenaline α1B/2C receptors | 5-HT1A, D2, 5-HT2A, adrenergic receptors | NCT06674694 | Approved |
| Olanzapine | Antagonist at multiple neurotransmitter receptors: dopamine D2, serotonin 5-HT2A, histamine H1, muscarinic M1–5, and adrenergic α1 receptors | D2, 5-HT2A, H1, muscarinic M1–5, α1-adrenergic receptors | NCT00088491 | Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
As a leader in rare neuropsychiatric disease research, Protheragen offers comprehensive preclinical services to advance schizophrenia therapeutics from discovery to validation. Our specialized platforms integrate genetic analysis and disease-specific modeling to replicate disease pathology with high fidelity. Using advanced blood-brain barrier (BBB) models, we optimize central nervous system (CNS) drug delivery while evaluating neuroprotection and off-target effects.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- Post-weaning Social Isolation Model
- Amphetamine Model
- PCP Model
- DISC-1 Knockout Model
- Dysbindin Knockout Model
- Other Models
Protheragen takes pride in offering comprehensive preclinical research services for schizophrenia using advanced disease models. These services encompass various aspects of drug research, including pharmacodynamics (PD), pharmacokinetics (PK), and safety evaluations, ensuring a holistic approach towards drug development in this challenging medical area. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Wani S N, Singh S, Sharma N, et al. Transferosome-based intranasal drug delivery systems for the management of schizophrenia: a futuristic approach[J]. BioNanoScience, 2024, 14(4): 3811-3829.
- Zhuo C, Tian H, Song X, et al. Microglia and cognitive impairment in schizophrenia: translating scientific progress into novel therapeutic interventions[J]. Schizophrenia, 2023, 9(1): 42.