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Reduction of the central effects of tryptophan by a decarboxylase inhibitor
Author(s) -
Hodge James V.,
Oates John A.,
Sjoerdsma Albert
Publication year - 1964
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt196452149
Subject(s) - tryptophan , monoamine oxidase inhibitor , decarboxylase inhibitor , serotonin , pharmacology , aromatic l amino acid decarboxylase , guinea pig , glutamate decarboxylase , chemistry , monoamine oxidase , medicine , endocrinology , biochemistry , enzyme , amino acid , levodopa , receptor , disease , parkinson's disease
Administration of L‐tryptophan to animals and man following monoamine oxidase inhibition produced characteristic neurological abnormalities which were chiefly excitatory in nature. Large doses of tryptophan in gUinea pigs also produced hyperpyrexia, and death followed in over 80 per cent of the animals. Pretreatment with a potent, centrally active decarboxylase inhibitor, Ro 4‐4602, diminished or prevented the neurological abnormalities abolished the hyperpyrexia in gUinea pigs, and reduced the animal mortality rate to below 10 per cent. Serotonin levels rose in the brains of guinea pigs after tryptophan but failed to do so when the tryptophan followed treatment with Ro 4‐4602. These results favor the conclusion that the effects seen after tryptophan administration are caused by its amine metabolites and not by the amino acid itself. The administration of L‐tryptophan to man under proper conditions provides a useful means of evaluating decarboxylase inhibition within the central nervous system in vivo and is the first such method to be described.