Methylene blue inhibits function of the 5-HT transporter

Research performed at:

1. Functional Lipidomics Branch, Department of Pharmacology.

2. Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, Al Ain, UAE.

3. Department of Cellular Biology & Pharmacology, College of Medicine, Florida International University, Miami, FL, USA.

4. Integrative Neuroscience Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, U.S. Department of Health and Human Services, Baltimore MD, USA.

The authors:

Murat Oz, Dmytro Isaev , Dietrich E Lorke, Muhammed Hasan, Georg Petroianu, and Toni S Shippenberg.

Methylene blue (MB) is commonly employed as a treatment for methaemoglobinaemia, malaria and vasoplegic shock. An increasing number of studies indicate that MB can cause 5-HT toxicity when administered with a 5-HT reuptake inhibitor. MB is a potent inhibitor of monoamine oxidases, but other targets that may contribute to MB toxicity have not been identified. Given the role of the 5-HT transporter (SERT) in the regulation of extracellular 5-HT concentrations, the present study aimed to characterize the effect of MB on SERT.

Live cell imaging, in conjunction with the fluorescent SERT substrate 4-(4-(dimethylamino)-styryl)-N-methylpyridinium (ASP+), [3H]5-HT uptake and whole-cell patch-clamp techniques were employed to examine the effects of MB on SERT function.

MB modulated SERT function and suggested that SERT may be an additional target upon which MB acts to produce 5-HT toxicity.