Repositioning of Omarigliptin as a once-weekly intranasal Anti-parkinsonian Agent PMID: 29895906

ADC Targets in Oncology

2026-04-10

Repositioning of Omarigliptin as a once-weekly intranasal Anti-parkinsonian Agent

Sci Rep. 2018 Jun 12;8(1):8959. doi: 10.1038/s41598-018-27395-0.

Bassam M Ayoub ¹ ² , Shereen Mowaka ³ ⁴ ⁵ , Marwa M Safar ⁴ ⁶ ⁷ , Nermeen Ashoush ⁴ ⁸ , Mona G Arafa ⁴ ⁹ ¹⁰ , Haidy E Michel ¹¹ , Mariam M Tadros ¹² , Mohamed M Elmazar ⁴ ⁶ , Shaker A Mousa ¹³

Affiliations

1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt. [email protected].
2. The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt. [email protected].
3. Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt.
4. The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt.
5. Analytical Chemistry Department, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo, Egypt.
6. Pharmacology & Biochemistry Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt.
7. Pharmacology & Toxicology Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini st., Cairo, Egypt.
8. Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt.
9. Pharmaceutics Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt.
10. Chemotheraputic Unit, Mansoura University Hospitals, Mansoura, 35516, Egypt.
11. Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, El-Abaseya, Cairo, Egypt.
12. Analytical Chemistry Department, Faculty of Pharmacy, Ain Shams University, El-Abaseya, Cairo, Egypt.
13. The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, United States.

Abstract

Drug repositioning is a revolution breakthrough of drug discovery that presents outstanding privilege with already safer agents by scanning the existing candidates as therapeutic switching or repurposing for marketed drugs. Sitagliptin, vildagliptin, saxagliptin & linagliptin showed antioxidant and neurorestorative effects in previous studies linked to DPP-4 inhibition. Literature showed that gliptins did not cross the blood brain barrier (BBB) while omarigliptin was the first gliptin that crossed it successfully in the present work. LC-MS/MS determination of once-weekly anti-diabetic DPP-4 inhibitors; omarigliptin & trelagliptin in plasma and brain tissue was employed after 2 h of oral administration to rats. The brain/plasma concentration ratio was used to deduce the penetration power through the BBB. Results showed that only omarigliptin crossed the BBB due to its low molecular weight & lipophilic properties suggesting its repositioning as antiparkinsonian agent. The results of BBB crossing will be of interest for researchers interested in Parkinson's disease. A novel intranasal formulation was developed using sodium lauryl sulphate surfactant to solubilize the lipophilic omarigliptin with penetration enhancing & antimicrobial properties. Intranasal administration showed enhanced brain/plasma ratio by 3.3 folds compared to the oral group accompanied with 2.6 folds increase in brain glucagon-like peptide-1 concentration compared to the control group.