Fenclonine: Difference between revisions

{{Short description|Chemical compound}}

| verifiedrevid = 449580729

| IUPAC_name = (''S'')-2-Amino-3-(4-chlorophenyl)propanoic acid

| image = Fenclonine.svg

| width = 150

| tradename =

| pregnancy_US = <!-- A / B / C / D / X -->

| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->

| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->

| IUPHAR_ligand = 5240

| CAS_number_Ref = {{cascite|correct|??}}

| ATC_prefix = None

| synonyms = CP-10188; Fenclonina; Fencloninum; NSC-77370; Parachlorophenylalanine<ref>"Fenclonine" entry in Martindale – The Complete Drug Reference. Maintained in Martindale purely for archival purposes, and is no longer subject to revision and update. (Last reviewed: 2008-08-01; last modified: 2011-09-12). The Royal Pharmaceutical Society of Great Britain 2014</ref>

| C=9 | H=10 | Cl=1 | N=1 | O=2

| solubility =

| melting_point = 240

| boiling_point = 339.5

| density = 1.336

'''Fenclonine''', also known as '''''para''-chlorophenylalanine''' ('''PCPA'''), acts as a selective and irreversible inhibitor of [[tryptophan hydroxylase]], which is a rate-limiting enzyme in the biosynthesis of [[serotonin]].<ref name=Jouvet>{{cite journal | vauthors = Jouvet M | title = Sleep and serotonin: an unfinished story | journal = Neuropsychopharmacology | volume = 21 | issue = 2 Suppl | pages = 24S–27S | date = August 1999 | pmid = 10432485 | doi = 10.1016/S0893-133X(99)00009-3 | doi-access = free }}</ref>

It has been used experimentally to treat [[carcinoid syndrome]], but the side effects, mostly hypersensitivity reactions and psychiatric disturbances, have prevented development for this use.<ref>{{cite journal | vauthors = Kvols LK | title = Metastatic carcinoid tumors and the carcinoid syndrome. A selective review of chemotherapy and hormonal therapy | journal = The American Journal of Medicine | volume = 81 | issue = 6B | pages = 49–55 | date = December 1986 | pmid = 2432781 | doi = 10.1016/0002-9343(86)90584-x }}</ref>

The effects of serotonin depletion from fenclonine are so drastic that serotonin cannot even be detected [[Histology|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 nuclei|raphe nucleus]], and after two weeks from initial treatment as much was again detected in the hypothalamus region. [[Aromatic L-amino acid decarboxylase|Aromatic <small>L</small>-amino acid decarboxylase]] (AADC) levels were at no time affected.<ref>{{cite journal | vauthors = Park DH, Stone DM, Baker H, Kim KS, Joh TH | title = Early induction of rat brain tryptophan hydroxylase (TPH) mRNA following parachlorophenylalanine (PCPA) treatment | journal = Brain Research. Molecular Brain Research | volume = 22 | issue = 1–4 | pages = 20–8 | date = March 1994 | pmid = 8015380 | doi = 10.1016/0169-328x(94)90028-0 }}</ref>

It is used in scientific research in humans<ref>{{cite journal | vauthors = Ruhé HG, Mason NS, Schene AH | title = Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies | journal = Molecular Psychiatry | volume = 12 | issue = 4 | pages = 331–59 | date = April 2007 | pmid = 17389902 | doi = 10.1038/sj.mp.4001949 | doi-access = }}</ref> and animals<ref name=Jouvet /> to investigate the effects of serotonin depletion.

== See also ==

* [[Metirosine|α-Methyl-''para''-tyrosine]] (AMPT, metirosine)

* [[Telotristat ethyl]] (Xermelo)

* [[AGN-2979]]

== References ==

{{Reflist|30em}}

{{Monoamine metabolism modulators}}

[[Category:Alpha-Amino acids]]

[[Category:Chloroarenes]]