Fenclonine, also known as ''para''-chlorophenylalanine (PCPA), acts as a selective and irreversible inhibitor of
tryptophan hydroxylase
Tryptophan hydroxylase (TPH) is an enzyme () involved in the synthesis of the neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-dependent aromat ...
, which is a rate-limiting enzyme in the biosynthesis of
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
.
It has been used experimentally to treat
carcinoid syndrome
Carcinoid syndrome is a paraneoplastic syndrome comprising the signs and symptoms that occur secondary to carcinoid tumors. The syndrome includes flushing and diarrhea, and less frequently, heart failure, vomiting and bronchoconstriction. It is ...
, but the side effects, mostly hypersensitivity reactions and psychiatric disturbances, have prevented development for this use.
The effects of serotonin depletion from fenclonine are so drastic that serotonin cannot even be detected
immunohistochemically within the first day after administration of a control dose. Tryptophan hydroxylase activity can be detected neither in cell bodies or nerve terminals. After one week 10% of control values (the baseline extrapolated for the study) had replenished in the
raphe nucleus, and after two weeks from initial treatment as much was again detected in the hypothalamus region.
Aromatic L-amino acid decarboxylase (AADC) levels were at no time affected.
It is used in scientific research in humans
and animals
to investigate the effects of serotonin depletion.
See also
*
α-Methyl-''para''-tyrosine (AMPT, metirosine)
*
''para''-Chloroamphetamine (PCA)
*
Telotristat ethyl
Telotristat ethyl (USAN, brand name Xermelo) is a prodrug of telotristat, which is an inhibitor of tryptophan hydroxylase. It is formulated as telotristat etiprate — a hippurate salt of telotristat ethyl.
On February 28, 2017, the U.S. Food a ...
(Xermelo)
*
AGN-2979
AGN-2979 is a glutarimide tryptophan hydroxylase activation inhibitor. It shows antidepressant properties in rodent models of Depression (mood), depression.
References
Glutarimides
O-methylated phenols
Tryptophan hydroxylase inhibitors ...
References
Amino acid derivatives
Chloroarenes
Tryptophan hydroxylase inhibitors
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