Brain stem tryptophan hydroxylase

Fig. (1). Reaction carried out by the enzyme tryptophan hydroxylase. Tryptophan is supplied by dietary intake and transported actively to the central nervous system (CNS). Tryptophan hydroxylase is the key enzyme controlling the synthesis of serotonin and is predominantly present in neurons located in the raphe nuclei of the brain stem...

Toloxatone (94) antagonized reserpine and potentiated the effects of trypt-amine and 5-HTP but not of DOPA. It had no amphetamine like, anticholiner c, antihistaminic or MAO inhibiting properties [251-253]. A later study showed that the compound was characterized by two agonistic effects activation of tryptophan hydroxylase (in vitro) and an inhibition of MAO activity in the rat brain stem, with 5>HT used as a substrate. A possible interaction in the catecholamine pathways was not excluded [254]. 

A relationship between substantia nigra lesions, striatal DA and movement disturbance was demonstrated by making unilateral lesions in the ventromedial tegmentum of the upper brain stem. This caused loss of cells in the substantia nigra, decrease of striatal DA and NA but not 5HT and contralateral hypokinesis [130, 131]. If lesions were made in dorsomedial fibres of the cerebral peduncle then striatal 5HT decreased [132]. Lesions of the above types cause not only depletion of the amines but also of the enzymes necessary for their synthesis, tyrosine hydroxylase, tryptophan hydroxylase and aromatic amino acid decarboxylase [133, 134]. 

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