N-acetyl-L-tryptophan (NAT) has been often shown to have neuroprotective action and other biological activities. In many of papers devoted to this compound, NAT is referenced to as an 'NK1 receptor (NK1R) antagonist' or a 'substance P (SP) antagonist'. Some of the studies treated NAT as a tool compound to interrogate NK1R function in a particular condition. Surprisingly however, no biochemical data on NAT/NK1R interaction have been available. On testing NAT in radioligand receptor binding assay, we found that this compound displays no significant binding to either human or rat NK1R up to millimolar concentrations. In light of this, the repeated claim of NAT being NK1R antagonist is an error. The use of NAT as a tool compound in NK1R-related studies should be discontinued. Some of the conclusions regarding the involvement of SP/NK1R axis in acute CNS injury or neurodegenerative diseases may then require careful rethinking. On the other hand, given interesting neuroprotective properties of NAT, the issue whether it acts by specific interactions with some molecular target or by unspecific physicochemical mechanisms needs be investigated.
Keywords: CNS injury; N-acetyl-L-tryptophan; Neurodegenerative diseases; Neurokinin-1 receptor; Neuroprotection; Substance P.
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