Depression
Central challenges in treating depression lie in the high prevalence of treatment-resistant cases and the enormous heterogeneity in the underlying neurobiology of the disorder. To address the complexities of managing depression, Protheragen offers comprehensive support services to streamline your process from drug candidate development to market launch.
Overview of Depression
Depression, clinically known as major depressive disorder (MDD), is a common but serious mood disorder characterized by persistent sadness, feelings of hopelessness, and a loss of interest or pleasure in activities once enjoyed. It is often accompanied by cognitive impairment, changes in sleep or appetite, low energy, and, in severe cases, even thoughts of death or suicide. Depression is highly prevalent worldwide, significantly impacting daily life and quality of life.
Fig.1 The pathogenesis of depression. (Yang Y H, et al., 2024)
Pathogenesis of Depression
Depression arises from a convergence of chronic stress-driven hypothalamic–pituitary–adrenal axis dysregulation, monoamines (especially serotonin, norepinephrine, dopamine) depletion, glutamate excitotoxicity, limbic inflammatory cytokine release, and stress- or age-related hippocampal volume loss, all further shaped by heritable polymorphisms in neuroplasticity genes.
Fig.2 An outline map of the hypotheses to explain major depressive disorder (MDD) pathogenesis. (Cui L, et al., 2024)
Therapeutic Development for Depression
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Sertraline | Selective serotonin re-uptake inhibition increases synaptic 5-HT. | Sodium-dependent serotonin transporter (SERT) | Approved |
| Duloxetine | Dual SERT & NET inhibition raises 5-HT & NE in synaptic cleft. | SERT, NET (and indirectly DAT in prefrontal cortex) | Approved |
| Amitriptyline | Non-selective monoamine re-uptake blockade plus antagonism at multiple receptors. | SERT, NET, plus H1, α1-adrenergic, M1 receptors | Approved |
| Mirtazapine | Enhances central noradrenergic & serotonergic transmission via α2-adrenergic antagonism and 5-HT2/3 receptor blockade. | α2A/B-adrenergic autoreceptors, 5-HT2A/2C & 5-HT3 receptors | Approved |
| Trazodone | 5-HT2A/C antagonist & SERT inhibitor that boosts 5-HT while limiting receptor overstimulation. | 5-HT2A/C receptors, SERT, α1-adrenergic receptors | 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 preclinical research service provider for depression, Protheragen provides end-to-end diagnostic and therapeutic development solutions. We excel in building physiologically relevant models, including in vitro models, animal models, and specialized blood-brain barrier (BBB) models, to enable comprehensive biomarker discovery, target validation, and CNS drug efficacy optimization.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- Acute Stress Model
- Learned Helplessness Model
- SERT Knockout Model
- α2A Adrenergic Receptor Knockout Model
- Forebrain Glucocorticoid Receptor Knockout Model
Protheragen is steadfastly dedicated to meticulously validating and optimizing therapies for depression through a thorough series of pharmacodynamics (PD), pharmacokinetics (PK) and toxicology studies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Yang Y H, Li C X, Zhang R B, et al. A review of the pharmacological action and mechanism of natural plant polysaccharides in depression[J]. Frontiers in Pharmacology, 2024, 15: 1348019.
- Cui L, Li S, Wang S, et al. Major depressive disorder: hypothesis, mechanism, prevention and treatment[J]. Signal transduction and targeted therapy, 2024, 9(1): 30.