Effects of amitriptyline on rat plasma and brain content of monoamine precursors and other large neutral amino acids.

Amitriptyline caused decreased concentrations in rat plasma of the amino acids tyrosine and tryptophan, which are precursors to monoaminergic neurotransmitters, and also of those other large neutral amino acids (LNAAs) (valine, phenylalanine, leucine and isoleucine) with which tyrosine and tryptophan compete for the carrier-mediated transport from plasma into the brain. The various LNAAs were, however, not decreased to the same extent. Thus, the relative concentrations, calculated as the ratio of each one of them to the total concentration of LNAAs, were also influenced by amitriptyline. The relative concentrations of tryptophan were decreased while the relative concentrations of phenylalanine and leucine were increased. Those of tyrosine, valine and isoleucine were not influenced by amitriptyline. The relative concentrations of the LNAAs in plasma are considered to be of importance to how much of each of them that will be transported into the brain. Based on this assumption one would have expected that the amitriptyline-induced changes in the relationships between different LNAAs would have caused changes in their brain concentrations in accordance with their relative concentrations in plasma. However, amitriptyline caused decreased concentrations of all LNAAs in rat whole brain. This finding cannot be explained by altered relationships between the LNAAs but must be explained by other mechanisms. Nevertheless, this effect of amitriptyline on brain LNAA concentrations might be of importance to monoamine function.