Preclinical Evaluation of Soluble Epoxide Hydrolase Inhibitor AMHDU against Neuropathic Pain
Abstract
:1. Introduction
2. Results
2.1. Anti-Inflammatory and Analgesic Activity
2.2. Pharmacokinetics Nature of the Molecule
2.3. Acute Oral Toxicity Results
3. Discussion
4. Materials and Methods
4.1. General
4.2. Anti-Inflammatory and Analgesic Activity Study
4.3. Tactile Allodynia Evaluation
4.4. Pharmacokinetic Study
4.5. Acute Oral Toxicity Study
4.6. Data Analysis and Statistics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Animal No. | Dose (mg/kg) | Cmax (ng/mL) | Tmax (h) | AUClast (ng/mL × h) | Thalf (h) | MRT (h) |
---|---|---|---|---|---|---|
1 | 1 | 24.32 | 2.0 | 24 | 0.18 | 1.51 |
2 | 1 | 53.00 | 0.5 | 35 | 0.16 | 1.04 |
3 | 1 | 31.93 | 1.0 | 31 | 0.13 | 1.08 |
4 | 1 | 30.86 | 0.5 | 16 | 0.15 | 0.55 |
m ± SE | 35.0 ± 12.4 | 1.0 | 26.4 ± 8.6 | 0.16 ± 0.02 | 1.1 ± 0.4 |
Mass Ratio to Whole Body Weight (%) | Group | ||
---|---|---|---|
Vehicle (n = 6) | 300 mg/kg AMHDU (n = 6) | 2000 mg/kg AMHDU (n = 3) | |
Brain | 0.72 ± 0.02 | 0.72 ± 0.02 (–0.1) | 0.72 ± 0.02 (–0.3) |
Heart | 0.36 ± 0.01 | 0.33 ± 0.01 (–6.4) | 0.32 ± 0.01 (–10.4) |
Lungs | 0.63 ± 0.03 | 0.60 ± 0.04 (–3.5) | 0.56 ± 0.03 (–10.7) |
Liver | 2.96 ± 0.18 | 3.03 ± 0.12 (2.1) | 2.77 ± 0.41 (–6.4) |
Kidneys | 0.64 ± 0.03 | 0.62 ± 0.02 (–3.1) | 0.64 ± 0.03 (0.4) |
Thymus | 0.18 ± 0.02 | 0.17 ± 0.03 (–4.1) | 0.16 ± 0.01 (–11.0) |
Spleen | 0.47 ± 0.05 | 0.48 ± 0.01 (0.5) | 0.43 ± 0.02 (–9.9) |
Adrenal glands | 0.04 ± 0.003 | 0.04 ± 0.004 (–8.5) | 0.03 ± 0.003 (–14.4) |
Ovaries | 0.05 ± 0.004 | 0.05 ± 0.003 (–1.0) | 0.06 ± 0.01 (18.3) |
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Babkov, D.; Eliseeva, N.; Adzhienko, K.; Bagmetova, V.; Danilov, D.; McReynolds, C.B.; Morisseau, C.; Hammock, B.D.; Burmistrov, V. Preclinical Evaluation of Soluble Epoxide Hydrolase Inhibitor AMHDU against Neuropathic Pain. Int. J. Mol. Sci. 2024, 25, 8841. https://doi.org/10.3390/ijms25168841
Babkov D, Eliseeva N, Adzhienko K, Bagmetova V, Danilov D, McReynolds CB, Morisseau C, Hammock BD, Burmistrov V. Preclinical Evaluation of Soluble Epoxide Hydrolase Inhibitor AMHDU against Neuropathic Pain. International Journal of Molecular Sciences. 2024; 25(16):8841. https://doi.org/10.3390/ijms25168841
Chicago/Turabian StyleBabkov, Denis, Natalya Eliseeva, Kristina Adzhienko, Viktoria Bagmetova, Dmitry Danilov, Cynthia B. McReynolds, Christophe Morisseau, Bruce D. Hammock, and Vladimir Burmistrov. 2024. "Preclinical Evaluation of Soluble Epoxide Hydrolase Inhibitor AMHDU against Neuropathic Pain" International Journal of Molecular Sciences 25, no. 16: 8841. https://doi.org/10.3390/ijms25168841