A COMPARISON OF d AND l‐TRYPTOPHAN ON THE CEREBRAL METABOLISM OF 5‐HYDROXYTRYPTAMINE AND DOPAMINE IN THE DOG

Abstract

After d and l‐tryptophan (50 mg/kg) were given intravenously in the dog, the concentration of the amino acid was increased in ventricular cerebrospinal fluid (CSF) during the subsequent 4 h of sampling, although the concentrations were significantly lower following the administration of the d‐isomer. There was no evidence that d‐tryptophan increased the synthesis of 5‐hydroxytryptamine (5‐HT) in dog brain as judged by the failure to cause a change in 5‐hydroxyindoleacetic acid (5‐HIAA) concentrations in ventricular CSF different from that seen with controls. There was no appreciable conversion of d‐tryptophan to l‐tryptophan in the dog. d‐tryptophan was cleared more rapidly from plasma than l‐tryptophan. No difference in plasma binding between d and l‐tryptophan was detected.

Blockade of mini-TrpRS for treatment of diabetic foot syndrome

“…Chemically, D-tryptophan is an enantiomer of L-tryptophan, an essential amino acid found in most human proteins, and a precursor to the neurotransmitter serotonin, the hormone melatonin, and vitamin B3 [15]. In experimental models, D-tryptophan is readily cleared from plasma, and there is no appreciable conversion of D-tryptophan to metabolically active L-tryptophan [16,17]. As such, side effects such as unintended stimulation of serotonin production in the brain [16] or other metabolic functions of the L-tryptophan [17] would be expected to be negligible in treated patients with a diabetic foot ulcer.…”

“…In experimental models, D-tryptophan is readily cleared from plasma, and there is no appreciable conversion of D-tryptophan to metabolically active L-tryptophan [16,17]. As such, side effects such as unintended stimulation of serotonin production in the brain [16] or other metabolic functions of the L-tryptophan [17] would be expected to be negligible in treated patients with a diabetic foot ulcer. Indeed, D-tryptophan, also known as NLG8189 and Indoximod (methylated D-tryptophan), has not been trialled exactly in patients with diabetic foot syndrome but oncological patients; the drug was investigated at a dose up to 2,000 mg twice daily, was well tolerated, and no patients discontinued treatment due to toxicity [18].…”