関: p-chlorophenylalanine

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/06 08:46:59」(JST)

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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.^[2]

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.^[3]

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.^[4]

It is used in scientific research in humans^[5] and animals^[2] to investigate the effects of serotonin depletion.

References

^ "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
^ ^a ^b Jouvet M Sleep and serotonin: an unfinished story. Neuropsychopharmacology. 1999 Aug;21(2 Suppl):24S-27S. PMID 10432485
^ Kvols LK. Metastatic carcinoid tumors and the carcinoid syndrome. A selective review of chemotherapy and hormonal therapy. (Am J Med. 1986 Dec 22;81(6B):49-55. PMID 2432781
^ Early induction of rat brain tryptophan hydroxylase (TPH) mRNA following parachlorophenylalanine (PCPA) treatment. Brain Res Mol Brain Res. 1994 Mar;22(1-4):20-8. PMID 8015380
^ Ruhé HG, Mason NS, Schene AH. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry. 2007 Apr;12(4):331-59. PMID 17389902

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English Journal

Tipepidine, a non-narcotic antitussive, exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone-treated rats.

Kawaura K1, Ogata Y1, Honda S1, Soeda F1, Shirasaki T1, Takahama K2.
Behavioural brain research.Behav Brain Res.2016 Apr 1;302:269-78. doi: 10.1016/j.bbr.2015.12.008. Epub 2015 Dec 29.
We investigated whether tipepidine exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone (ACTH)-treated rats, which is known as a treatment-resistant depression model, and we studied the pharmacological mechanisms of the effects of tipepidine. Male Wistar ra
PMID 26738969

Serotonin depletion eliminates sex differences with respect to context-conditioned immobility in rat.

Pettersson R1, Hagsäter SM1, Eriksson E2.
Psychopharmacology.Psychopharmacology (Berl).2016 Apr;233(8):1513-21. doi: 10.1007/s00213-016-4246-5. Epub 2016 Feb 24.
RATIONALE: Previous studies have shown that male rats display more anxiety-like behavior than females as assessed using the elevated plus maze and that serotonin depletion abolishes this difference by exerting an anxiolytic-like effect in males only.OBJECTIVES: To compare male and female rats with r
PMID 26905688

The Antidepressant Effects of an mGlu2/3 Receptor Antagonist and Ketamine Require AMPA Receptor Stimulation in the mPFC and Subsequent Activation of the 5-HT Neurons in the DRN.

Fukumoto K1, Iijima M1, Chaki S1.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.Neuropsychopharmacology.2016 Mar;41(4):1046-56. doi: 10.1038/npp.2015.233. Epub 2015 Aug 6.
We have reported the antidepressant effects of both metabotropic glutamate 2/3 (mGlu2/3) receptor antagonists and ketamine in several animal models, and proposed that serotonergic (5-HTergic) transmission is involved in these actions. Given that the projections from the medial prefrontal cortex (mPF
PMID 26245499

「p-chlorophenylalanine」

Fenclonine
Systematic (IUPAC) name
	(S)-2-amino-3-(4-chlorophenyl)propanoic acid
Identifiers
CAS Number	7424-00-2
ATC code	none
PubChem	CID 4652
IUPHAR/BPS	5240
ChemSpider	4491
UNII	R5J7E3L9SP
KEGG	D04143
Synonyms	CP-10188; Fenclonina; Fencloninum; NSC-77370; Parachlorophenylalanine
Chemical data
Formula	C9H10ClNO
Molar mass	199.634 g/mol
	SMILES Clc1ccc(cc1)CC(C(=O)O)N ;
	InChI InChI=1S/C9H10ClNO2/c10-7-3-1-6(2-4-7)5-8(11)9(12)13/h1-4,8H,5,11H2,(H,12,13) ; Key:NIGWMJHCCYYCSF-UHFFFAOYSA-N ;
Physical data
Density	1.336 g/cm3
Melting point	240 °C (464 °F)
Boiling point	339.5 °C (643.1 °F)
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