Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity—In Vitro and In Vivo Studies
Abstract
1. Introduction
2. Results and Discussion
2.1. In Vitro Assays
2.1.1. Antioxidant Activity
Cmpd. | R 1 | R 2 | Ar | FRAP (%AAA) 1 | ORAC (TE) 2 | [3H]AMPA Ki (μM) 3 |
---|---|---|---|---|---|---|
1 | NO2 | Cl | 2′,5′-diOH Ph | 748.49 | 3.46 | 0.92 |
2 | NO2 | Cl | 5′-OH-3-pyridyl | 691.21 | 3.15 | 2.0 |
3 | Cl | OH | 3′-OH Ph | 311.56 | 4.61 | 7.9 |
4 | Cl | Cl | 3′,4′-diOH Ph | 177.23 | 4.02 | 12 4 |
5 | NO2 | H | 4′-OH Ph | 96.32 | 4.32 | 21 |
6 | H | NH2 | 3′-OH Ph | 67.35 | 6.09 | 9.1 |
7 | Cl | H | 4′-OH Ph | 49.39 | 3.29 | 46 |
8 | Cl | NH2 | 4′-OH Ph | 48.19 | 7.56 | >100 |
9 | NO2 | H | 3′-OH Ph | 43.43 | 4.67 | 8.2 |
10 | H | NO2 | 3′-OH Ph | 32.04 | 1.43 | 21 |
11 | Cl | Cl | 3′,5′-diOH Ph | 28.90 | 4.18 | 16 4 |
12 | NO2 | NH2 | 3′-OH Ph | 24.93 | 4.27 | 14 |
13 | H | Cl | 3′-OH Ph | 24.08 | 2.86 | 9.2 |
14 | Cl | NH2 | 3′-OH Ph | 23.80 | 4.75 | 10 |
15 | Cl | Cl | 4′-OH Ph | 13.70 | 1.45 | 33 4 |
16 | Cl | Cl | 2′-OH Ph | 10.32 | 1.54 | 85 4 |
17 | H | Cl | 4′-OH Ph | 9.13 | 1.96 | 65 |
18 | NO2 | Cl | 3′-OH Ph | 6.29 | 1.34 | 3.1 |
19 | H | H | 3′-OH Ph | 4.94 | 1.96 | 9.9 4 |
20 | H | NO2 | 4′-OH Ph | 4.41 | 1.62 | 64 |
21 | NO2 | Cl | 4′-OH Ph | 2.76 | 2.56 | 23 |
22 | Cl | OCH3 | 3′-OH Ph | 2.76 | 1.38 | >100 |
2.1.2. Neuroprotection
2.1.3. ROS Assay
2.1.4. MAO-B Inhibition
2.2. In Vivo Assays
2.2.1. Anticonvulsant Activity in Seizure Models
- MES Test
- PTZ Seizure Test
- 6-Hz Test
2.2.2. Antiallodynic and Antihyperalgesic Activity in Neuropathic Pain Models
Diabetic Neuropathic Pain Model
- Effect on Tactile Allodynia—Von Frey Test
- Effect on Heat Hyperalgesia—Hot Plate Test
Oxaliplatin-Induced Neuropathic Pain Model
- Effect on Tactile Allodynia—Von Frey Test
- Effect on Cold Hyperalgesia—Cold Plate Test
3. Conclusions
4. Materials and Methods
4.1. In Vitro Assays
4.1.1. Antioxidant Activity
- FRAP
- ORAC-FL
4.1.2. Neuroprotection
- Cell Viability
- Lactate Dehydrogenase Test
- ROS Assay
4.1.3. MAO-B Inhibition
4.2. In Vivo Assays
4.2.1. Animals and Housing Conditions
4.2.2. Chemicals
4.2.3. Assessment of Anticonvulsant Activity
- Maximal Electroshock Test (MES Test)
- PTZ Test
- 6-Hz Test
4.2.4. Assessment of Antiallodynic and Antihyperalgesic Properties in Neuropathic Pain Models
Streptozotocin-Induced Painful Diabetic Neuropathy
- Induction of Diabetes
- Influence on Tactile Allodynia in Diabetic Mice—Von Frey Test
- Influence on Heat Hyperalgesia in Diabetic Mice—Hot Plate Test
Oxaliplatin-Induced Peripheral Neuropathy
- Induction of Neuropathy
- Influence on Tactile Allodynia in Oxaliplatin-Treated Mice—Von Frey Test
- Influence on Cold Hyperalgesia in Oxaliplatin-Treated Mice—Cold Plate Test
4.2.5. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Compound | Dose [mg/kg] | X/Y 1 | Mortality Rate (%) |
---|---|---|---|
Vehicle | - | 1/5 | 20 |
1 | 100 | 0/4 | 25 |
Compound | Dose [mg/kg] | X/Y 1 | Mortality rate (%) |
---|---|---|---|
Vehicle | - | 0/3 | 0 |
1 | 100 | 3/4 | 0 |
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Latacz, G.; Sałat, K.; Furgała-Wojas, A.; Martyniak, A.; Olejarz-Maciej, A.; Honkisz-Orzechowska, E.; Szymańska, E. Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity—In Vitro and In Vivo Studies. Molecules 2022, 27, 875. https://doi.org/10.3390/molecules27030875
Latacz G, Sałat K, Furgała-Wojas A, Martyniak A, Olejarz-Maciej A, Honkisz-Orzechowska E, Szymańska E. Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity—In Vitro and In Vivo Studies. Molecules. 2022; 27(3):875. https://doi.org/10.3390/molecules27030875
Chicago/Turabian StyleLatacz, Gniewomir, Kinga Sałat, Anna Furgała-Wojas, Adrian Martyniak, Agnieszka Olejarz-Maciej, Ewelina Honkisz-Orzechowska, and Ewa Szymańska. 2022. "Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity—In Vitro and In Vivo Studies" Molecules 27, no. 3: 875. https://doi.org/10.3390/molecules27030875
APA StyleLatacz, G., Sałat, K., Furgała-Wojas, A., Martyniak, A., Olejarz-Maciej, A., Honkisz-Orzechowska, E., & Szymańska, E. (2022). Phenylalanine-Based AMPA Receptor Antagonist as the Anticonvulsant Agent with Neuroprotective Activity—In Vitro and In Vivo Studies. Molecules, 27(3), 875. https://doi.org/10.3390/molecules27030875