Brain Delivery of Thyrotropin-Releasing Hormone via a Novel Prodrug Approach
Abstract
1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Instruments
2.3. Animals
2.4. Synthesis
2.5. Membrane Affinity Studies
2.6. In Vitro Metabolic Stability Studies
2.7. Neuropharmacodynamic Assesment: PST
2.8. Neurochemical Assestment: ACh Release Using In Vivo Microdialysis
2.9. Statistical Analysis
3. Results and Discussion
3.1. Synthesis and IAMC Studies
3.2. In Vitro Metabolic Stability Studies
3.3. In Vivo Studies
3.3.1. Antidepressant-Like Effect
3.3.2. ACh Release
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound | CHIIAM 1 | clogP 2 |
---|---|---|
TRH | −11.2 ± 3.2 | −3.50 |
(1) | 66.0 ± 10.3 | 1.85 |
Test Compound | t1/2 in Plasma | t1/2 in 20% (w/v) Brain Homogenate |
---|---|---|
TRH | 7 ± 4 min | 4 ± 1 min |
(1) | 100 ± 7 min | 47 ± 6 min |
(1) + KYP-2047 | 115 ± 13 min | >24 h |
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Prokai-Tatrai, K.; De La Cruz, D.L.; Nguyen, V.; Ross, B.P.; Toth, I.; Prokai, L. Brain Delivery of Thyrotropin-Releasing Hormone via a Novel Prodrug Approach. Pharmaceutics 2019, 11, 349. https://doi.org/10.3390/pharmaceutics11070349
Prokai-Tatrai K, De La Cruz DL, Nguyen V, Ross BP, Toth I, Prokai L. Brain Delivery of Thyrotropin-Releasing Hormone via a Novel Prodrug Approach. Pharmaceutics. 2019; 11(7):349. https://doi.org/10.3390/pharmaceutics11070349
Chicago/Turabian StyleProkai-Tatrai, Katalin, Daniel L. De La Cruz, Vien Nguyen, Benjamin P. Ross, Istvan Toth, and Laszlo Prokai. 2019. "Brain Delivery of Thyrotropin-Releasing Hormone via a Novel Prodrug Approach" Pharmaceutics 11, no. 7: 349. https://doi.org/10.3390/pharmaceutics11070349
APA StyleProkai-Tatrai, K., De La Cruz, D. L., Nguyen, V., Ross, B. P., Toth, I., & Prokai, L. (2019). Brain Delivery of Thyrotropin-Releasing Hormone via a Novel Prodrug Approach. Pharmaceutics, 11(7), 349. https://doi.org/10.3390/pharmaceutics11070349