Diuretic Activity of a Novel Peripherally-Restricted Orally-Active Kappa Opioid Receptor Agonist
| Autor: | Matthew A. Hapstack, Tyler Beck, Gautam S. Ghatnekar, Thomas A. Dix |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Agonist
medicine.drug_class medicine.medical_treatment diuretic Tolvaptan heart failure lcsh:Medicine Diuresis 030204 cardiovascular system & hematology Pharmacology κ-opioid receptor Article 03 medical and health sciences 0302 clinical medicine cardiovascular disease Oral administration Medicine cardiovascular diseases kappa agonist business.industry lcsh:R medicine.disease 3. Good health Opioid 030220 oncology & carcinogenesis Heart failure cardiovascular system opioid Diuretic business medicine.drug |
| Zdroj: | Medical Sciences, Vol 7, Iss 9, p 93 (2019) Medical Sciences Volume 7 Issue 9 |
| ISSN: | 2076-3271 |
| DOI: | 10.3390/medsci7090093 |
| Popis: | Kappa-opioid agonists (KOAs) enhance cardiac performance, as well as reduce infarct size and prevent deleterious cardiac remodeling following myocardial infarction. Additionally, KOAs promote diuresis however, there has been limited development of KOAs as a class due to the promotion of untoward central nervous system (CNS)-mediated side effects. Our laboratory has developed a peripherally-restricted, orally-active, KOA (JT09) for the treatment of pain and cardiovascular disease. Peripherally-restricted KOAs possess a limited side-effect profile and demonstrate potential in preventing heart failure. The aim of this study was to assess the diuretic activity of lead compound JT09 relative to vehicle control and Tolvaptan through single oral administration to adult male Sprague&ndash Dawley rats. JT09-administered rats demonstrated significantly increased urine output relative to vehicle control. However, the effect persisted for 8 h, whereas Tolvaptan-administered rats demonstrated diuretic activity for 24 h. Relative to Tolvaptan, urine output was significantly reduced in JT09 administered animals at all-time points, suggesting that the overall diuretic effect of JT09 is less profound than Tolvaptan. Additionally, JT09-administered rats demonstrated alterations in clinical chemistry reduced urine specific gravity and increased urine pH relative to vehicle control. The following study establishes a preliminary diuretic profile for JT09. |
| Databáze: | OpenAIRE |
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