Dantrolene: could intranasal administration penetrate the brain more effectively?

Written by Alice Bough (Future Science Group)

Researchers from the University of Pennsylvania Perelman School of Medicine (PA, USA) have determined that in mice, nasal administration of the muscle relaxant dantrolene allows the drug to remain in the brain for longer than when given orally.

The results of the study, published in PLOS One, present nasal administration of dantrolene as a potential long-term treatment option for neurodegenerative diseases.

Previous studies in cellular and animal models suggest that dantrolene can improve mental function and have therapeutic efficacy against neurodegenerative diseases such as Alzheimer’s. However, oral delivery of the muscle relaxant does not allow effective delivery into the central nervous system.

“We know the use of dantrolene in the treatment of Alzheimer’s disease or stroke would require chronic administration,” explained corresponding author of the paper, Huafeng Wei (University of Pennsylvania). “Rather than using high doses of the oral form, which could increase the risk of adverse side effects, we sought to test the effectiveness of the intranasal approach via pre-clinical studies in mice.”

The study involved two groups of mice, one of which received the oral form of dantrolene and another which received the intranasal form. The concentration of drug in the brain and the circulation was measured at different timepoints. For mice receiving the intranasal dantrolene, the medication remained in their brains for at least 180 minutes, while there was no drug found to be remaining after 120 minutes in the brains of mice that had received oral dantrolene.

You might also like:

This research builds upon a previous proof-of-concept study by Wei and colleagues that identified that if dantrolene was delivered nasally it was more effective at improving cognition and reducing memory loss in mice than if it had been administered subcutaneously.

To study the effects of chronic administration, mice were given intranasal dantrolene three-times a week for 4 months. Long-term exposure did not appear to affect the motor ability of the mice nor their ability to smell.

“While more research in animal models is needed to further evaluate the safety and effectiveness of this approach, our hope is that this will ultimately lead to a new therapeutic approach that can be studied in patients with various neurodegenerative diseases, including Alzheimer’s,” concluded Wei.

Source: www.eurekalert.org/emb_releases/2020-03/uops-gcm030620.php