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8722040 
Journal Article 
Estimation of melatonin blood brain barrier permeability 
Johns, J 
2011 
Yes 
Journal of Bioanalysis & Biomedicine
ISSN: 1948-593X 
3 
3 
64-69 
English 
Essentially 100% of large molecules and less than 2% of small molecules can cross the blood brain barrier (BBB). Thus there are a very limited number neuropharmaceuticals available. Currently there is great interest in melatonin for treatment of CNS disorders and its interaction with the CNS, mostly concerning its antioxidant properties. The ability of melatonin to pass the BBB has been attributed to its amphiphilic nature and octanol-water partition coefficient (logP oct = 1.2). Studies have found comparable levels of melatonin in cerebrospinal fluid and plasma after intravenous or intranasal administration. However the permeability of melatonin across the human BBB has not been quantified or studied by direct experimental methods. Previous research has also shown that logP oct is not a good model for predicting drug permeation of the BBB compared with cyclohexane-water partition coefficient (logP cyc) or other alkane partition coefficients. The objective of this study was to investigate blood-brain partitioning of exogenous melatonin using logP cyc). Firstly, the logP cyc and logP oct of melatonin were measured using the shake flask method and UV-spectrophotometry. Secondly, this was compared with predictions based on published logP oct/ logP cyc correlations for other drugs and calculated values. Lastly the melatonin BBB partition (log BB) was predicted from correlations of log BB with cyclohexane. The cyclohexane-water partition coefficient was found to be logP cyc = -1.15 ± 0.34 (P= 0.071) in phosphate buffer, pH = 7.4 at 28 oC. Thus melatonin has limited solubility in cyclohexane (14 times more soluble in water than cyclohexane). Based on the logP cyc, a predicted value of log BB = 0.096 ± 0.055 i.e. almost equal partitioning between blood and brain, implies melatonin can easily pass to the brain as previously experimentally observed, but permeability is lower than many drugs developed and targeted specifically for the brain. 2011 Johns J. 
Blood brain barrier; Cyclohexane; Melatonin; Octanol; Partition coefficient