Conjugation of sulpiride with a cell penetrating peptide to augment the antidepressant efficacy and reduce serum prolactin levels - 27/04/24
Abstract |
Depression ranks as the fourth most prevalent global disease, with suicide incidents occurring at a younger age. Sulpiride (SUL), an atypical antidepressant drug acting as a dopamine D2 receptor antagonist and possessing anti-inflammatory properties, exhibits limited ability to penetrate the blood brain barrier (BBB). This weak penetration hampers its inhibitory effect on prolactin release in the pituitary gland, consequently leading to hyperprolactinemia. In order to enhance the central nervous system efficacy of sulpiride and reduce serum prolactin levels, we covalently linked sulpiride to VPALR derived from the nuclear DNA repair protein ku70. In vivo study on depressive mice using intraperitoneal injection of VPALR-SUL demonstrated a significant increase in struggle time and total distance compared to those treated with only sulpiride while also reducing serum prolactin concentration. The pharmacokinetic study results showed that VPALR-SUL prolonged half-life and increased bioavailability. In conclusion, VPALR-SUL exhibited potential for enhancing sulpiride transport across the BBB, augmenting its antidepressant effects, and reducing serum prolactin levels. This study laid a foundation for improving sulpiride delivery and developing novel antidepressants.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Schematic diagram of the conjugation of sulpiride with a cell-penetrating peptide to augment the antidepressant efficacy and diminish serum prolactin levels.
Schematic diagram of the conjugation of sulpiride with a cell-penetrating peptide to augment the antidepressant efficacy and diminish serum prolactin levels.Le texte complet de cet article est disponible en PDF.
Highlights |
• | Conjugation of sulpiride with a cell-penetrating peptide VPALR for antidepressant. |
• | VPALR-SUL augmented the antidepressant efficacy and diminished serum prolactin levels. |
• | VPALR-SUL exhibited potential for enhancing sulpiride transport across the blood-brain barrier. |
• | VPALR-SUL increased struggle time and total distance compared to those treated with sulpiride. |
• | This study laid a foundation for developing novel antidepressants. |
Keywords : Sulpiride, Cell penetrating peptide, Depression, Hyperprolactinemia, Pharmacokinetic study
Plan
Vol 174
Article 116610- mai 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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