Tryptophan hydroxylase (L-tryptophan, tetrahydropteridine:oxygen oxidoreductase 
[5-hydroxylating]; EC 1.14.16.4; TPH), the initial and rate-limiting enzyme in 
the biosynthesis of the neurotransmitter serotonin, was inhibited directly by 
benserazide, an inhibitor of aromatic-L-amino-acid decarboxylase 
(3,4-dihydroxy-L-phenylalanine carboxy-lyase; EC 4.1.1.28; AAAD). Benserazide 
was a competitive inhibitor for the pterin cofactor tetrahydrobiopterin and an 
uncompetitive inhibitor for the substrate tryptophan. NSD 1015, another 
decarboxylase inhibitor, did not directly inhibit TPH. Other compounds with 
catechol moieties in their structures such as 3,4-dihydroxyphenylalanine (DOPA), 
dopamine, apomorphine, and SKF 38393 were also found to be potent inhibitors of 
TPH. These results indicate that drugs or neurotransmitters with catechol 
structures directly inhibit the activity of TPH and add to a growing body of 
evidence indicating that endogenous dopamine can exert untoward effects on 
serotonin neurons, including inhibition of TPH. Furthermore, the use of 
decarboxylase inhibitors to cause the accumulation of 5-hydroxytryptophan as an 
in vivo measure of TPH activity could be problematic, particularly when drugs 
with catechol structures or dopamine-releasing compounds are also administered.