Effect of combined administration of tryptophan with putative tryptophan pyrrolase inhibitors, DL-3-pyridylalanine, allopurinol or nicotinamide, on brain serotonin concentration.

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1) Single administration of tryptophan (25-200 mg / kg) to Wistar male rats resulted in a dose-related increase in liver tryptophan pyrrolase (TP) activity. The increase in brain serotonin (5-HT) concentration was not proportional to the dose given, and brain 5-HT concentration rapidly fell to the control (saline-treated) level or below. 2) The tryptophan-induced increase in liver TP activity was clearly prevented by DL-3-pyridylalanine (3-PA, 100 mg/kg). Serum free tryptophan and brain 5-HT concentrations increased more markedly and maintained higher levels after the combined administration of tryptophan with 3-PA than after a single administration of tryptophan. 3) Although allopurinol (20 mg/kg) reduced liver TP activity under control and tryptophan-treated conditions, it did not increase serum free tryptophan and brain 5-HT concentrations. 4) Nicotinamide also failed to alter the catabolism of tryptophan and the concentration of brain 5-HT in control or tryptophan-treated rats. 5) These data suggest that 3-PA would increase the therapeutic effect of tryptophan given to treat depressive illness, but that allopurinol and nicotinamide would not be suitable drugs for this purpose.