Analgesic effects of N-acetyl-5HTP-5HTP amide are not directly related to brain serotonin levels.

A synthetic dipeptide, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide, was shown previously to inhibit the binding of serotonin to a soluble specific serotonin binding protein as well as to alter brain serotonin levels. When injected into rats intraventricularly, the dipeptide caused an increase in pain threshold, lasting for several hours, as determined by either a flinch-jump test or a tail-flick test. This effect was reversed by naloxone. The dipeptide is a very weak inhibitor of the binding of labelled naloxone or dihydromorphine to a membranous opiate receptor preparation. The analgesic activity of the dipeptide was not diminished by p-chlorophenylalanine or the setonergic neurotoxin 5,7-dihydroxytryptamine, which depleted brain serotonin levels. This implies that the analgesic action of the dipeptide is not mediated directly by its effect on serotonin concentration.