Fenclonine

{{Short description|Chemical compound}}

{{Drugbox

| Watchedfields = changed

| verifiedrevid = 449580729

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

| image = Fenclonine.svg

| image_class = skin-invert-image

| width = 150

| tradename =

| pregnancy_AU =

| pregnancy_US =

| legal_AU =

| legal_CA =

| legal_UK =

| legal_US =

| IUPHAR_ligand = 5240

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

| CAS_number = 7424-00-2

| ATC_prefix = None

| PubChem = 4652

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 4491

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = R5J7E3L9SP

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D04143

| synonyms = CP-10188; Fenclonina; Fencloninum; NSC-77370; Parachlorophenylalanine"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

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

| solubility =

| melting_point = 240

| boiling_point = 339.5

| density = 1.336

| smiles = Clc1ccc(cc1)CC(C(=O)O)N

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C9H10ClNO2/c10-7-3-1-6(2-4-7)5-8(11)9(12)13/h1-4,8H,5,11H2,(H,12,13)

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = NIGWMJHCCYYCSF-UHFFFAOYSA-N

}}

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.{{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 }}

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.{{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 }}

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.{{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 }}

It is used in scientific research in humans{{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 = }} and animals to investigate the effects of serotonin depletion.