関: hydroxyamphetamine

WordNet

send a message from one computer to another to check whether it is reachable and active; "ping your machine in the office"
a sharp high-pitched resonant sound (as of a sonar echo or a bullet striking metal)
contact, usually in order to remind of something; "Ill ping my accountant--April 15 is nearing"
hit with a pinging noise; "The bugs pinged the lamp shade"
make a short high-pitched sound; "the bullet pinged when they struck the car"
the 16th letter of the Roman alphabet (同)p

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(小銃弾などの)ピュー(ブーン)という音 / ピュー(ブーン)と音がする
parking
phosphorusの化学記号

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/11 03:58:49」(JST)

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4-Hydroxyamphetamine (4HA), also known as hydroxyamfetamine (INN and BAN), hydroxyamphetamine (USAN), oxamphetamine, norpholedrine, para-hydroxyamphetamine, and α-methyltyramine, is a sympathomimetic drug, that is, a drug that stimulates the sympathetic nervous system.

It is used medically in eye drops to dilate the pupil (a process called mydriasis), so that the back of the eye can be examined. It is also a major metabolite of amphetamine and certain substituted amphetamines.

Medical use

4-Hydroxyamphetamine is used in eye drops to dilate the pupil (a process called mydriasis) so that the back of the eye can be examined. This is a diagnostic test for Horner's Syndrome. Patients with Horner’s syndrome exhibit anisocoria brought about by lesions on the nerves that connect to the nasociliary branch of the ophthalmic nerve.^[1] Application of 4-hydroxyamphetamine to the eye can indicate whether the lesion is preganglionic or postganglionic based on the pupil’s response. If the pupil dilates, the lesion is preganglionic. If the pupil does not dilate, the lesion is postganglionic.^[1]

4-hydroxyamphetamine has some limitations to its use as a diagnostic tool. If it is intended as an immediate follow up to another mydriatic drug (cocaine or apraclonidine), then the patient must wait anywhere from a day to a week before 4-hydroxyamphetamine can be administered.^[2]^[3] It also has the tendency to falsely localize lesions. False localization can arise in cases of acute onset; in cases where a postganglionic lesion is present, but the nerve still responds to residual norepinephrine; or in cases in which unrelated nerve damage masks the presence of a preganglionic lesion.^[1]^[2]

Pharmacology

Like amphetamine, 4-hydroxyamphetamine is an agonist of human TAAR1.^[4] 4-Hydroxyamphetamine acts as an indirect sympathomimetic and causes the release of norepinephrine from nerve synapses which leads to mydriasis.^[3]^[5]

It decreases metabolism of serotonin (5-hydroxytryptamine) and certain other monoamines by inhibiting the activity of a family of enzymes called monoamine oxidases (MAOs), particularly type A (MAO-A). The inhibition of MAO-A prevents metabolism of serotonin and catecholamines in the presynaptic terminal, and thus increases the amount of neurotransmitters available for release into the synaptic cleft.^[6] 4-Hydroxyamphetamine is a major metabolite of amphetamine and a minor metabolite of methamphetamine. In humans, amphetamine is metabolized to 4-hydroxyamphetamine by CYP2D6, which is a member of the cytochrome P450 superfamily and is found in the liver.^[7]^[8] 4-Hydroxyamphetamine is then metabolized by dopamine beta-hydroxylase into 4-hydroxynorephedrine or eliminated in the urine.^[5]

Metabolic pathways of amphetamine

4-Hydroxyphenylacetone

Phenylacetone

Benzoic acid

Hippuric acid

Amphetamine

Norephedrine

4-Hydroxyamphetamine

4-Hydroxynorephedrine

Para-
Hydroxylation

Beta-
Hydroxylation

Oxidative
Deamination

Oxidation

Glycine
Conjugation

In humans, 4-hydroxyamphetamine is formed from CYP2D6 metabolism of amphetamine; 4-hydroxyamphetamine may subsequently be metabolized by dopamine β-hydroxylase into 4-hydroxynorephedrine.

Commercialization

Hydroxyamphetamine is a component of two controlled (prescription only), name-brand ophthalmic mydriatics: Paredrine and Paremyd. Paredrine consists of a 1% solution of hydroxyamphetamine hydrobromide^[9]^:543 while Paremyd consists of a combination of 1% hydroxyamphetamine hydrobromide and 0.25% tropicamide.^[10] In the 1990s, the trade name rights, patents, and new drug applications (NDAs) for the two formulations were exchanged among a few different manufacturers after a shortage of the raw material required for their production, which caused both drugs to be indefinitely removed from the market.^[11] Around 1997, Akorn, Inc., obtained the rights to both Paredrine and Paremyd,^[12] and in 2002, the company reintroduced Paremyd to the market as a fast acting ophthalmic mydriatic agent.^[10]^[13]^[14]

References

^ ^a ^b ^c Walton KA & Buono LM (2003). "Horner syndrome." Current opinion in ophthalmology. 14(6):357 PMID 14615640
^ ^a ^b Davagnanam I, Fraser CL, Miszkiel K, Daniel CS, & Plant GT (2013). "Adult Horner's syndrome: a combined clinical, pharmacological, and imaging algorithm." Eye (London, England). 27(3):291,294 PMID 23370415
^ ^a ^b Lepore FE (1985). "Diagnostic pharmacology of the pupil." Clinical neuropharmacology. 8(1):29 PMID 3884149
^ "Articleid 50034244". Binding Database. Retrieved 29 April 2014.
^ ^a ^b Cho AK & Wright J (1978). "Pathways of metabolism of amphetamine and related compounds." Life sciences. 22(5):368 PMID 347211
^ Nakagawasai O, et al. (2004). "Monoamine oxidase and head-twitch response in mice. Mechanisms of alpha-methylated substrate derivatives." Neurotoxicology. 25(1-2):223-232 PMID 14697897
^ Markowitz JS & Patrick KS (2001). "Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder." Clinical pharmacokinetics. 40(10):757-758 PMID 11707061
^ Haefely W, Bartholini G, & Pletscher A (1976). "Monoaminergic drugs: general pharmacology." Pharmacology & therapeutics. Part B: General & systematic pharmacology. 2(1):197 PMID 817330
^ Slamovits TL and JS Glaser. 'The Pupils and Accommodation." in Neuro-ophthamology, ed Glaser JS. Lippincott, Williams, & Wilkins; Philadelphia, PA, 1999. ISBN 978-0781717298
^ ^a ^b Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations
^ Akorn press release. March 24, 1999. Akorn Acquires Paredrine - Specialty Ophthalmic Diagnostic Product From Pharmics, Inc.
^ Akorn press release
^ Akorn timeline Page accessed December 9, 2014
^ Rebecca Lurcott for Ophthalmology Management. December 1, 2002 Unique Mydriatic Returns: The combination formula fosters patient flow efficiencies

External links

p-Hydroxyamphetamine at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. ホルネル症候群 horner syndrome

English Journal

Species differences in the metabolism of ritobegron in vitro and assessment of potential interactions with transporters and cytochrome P450 enzymes.

Abe Y, Ota E, Harada H, Kanbe H, Kojima Y, Kanazawa T, Endo T, Murakami M, Kobayashi M.
Die Pharmazie.Pharmazie.2015 Jan;70(1):38-46.
Ritobegron, a selective β3-adrenoceptor agonist, is the prodrug of the active compound, KUC-7322. We investigated species differences in its metabolism in vitro and the potential for drug-drug interactions with ritobegron. In rat, dog, monkey, and human liver microsomes, ritobegron was not metaboli
PMID 25975097

Absorption, disposition, metabolism, and excretion of ritobegron (KUC-7483), a novel selective β3-adrenoceptor agonist, in rats.

Abe Y, Ota E, Endo T, Murakami M, Kobayashi M.
Die Pharmazie.Pharmazie.2014 Dec;69(12):881-8.
The pharmacokinetic profile of ritobegron, a novel, selective β3-adrenoceptor agonist, was investigated in rats. Ritobegron, an ethyl ester prodrug of the active compound KUC-7322, or KUC-7322 itself was orally administered (10 mg/kg). Ethyl esterification resulted in a 10-fold increase in the area
PMID 25951660

Adult Horner's syndrome: a combined clinical, pharmacological, and imaging algorithm.

Davagnanam I1, Fraser CL, Miszkiel K, Daniel CS, Plant GT.
Eye (London, England).Eye (Lond).2013 Mar;27(3):291-8. doi: 10.1038/eye.2012.281. Epub 2013 Feb 1.
The diagnosis of Horner's syndrome (HS) can be difficult, as patients rarely present with the classic triad of ptosis, miosis, and anhydrosis. Frequently, there are no associated symptoms to help determine or localise the underlying pathology. The onset of anisocoria may also be uncertain, with many
PMID 23370415

Japanese Journal

Repeated Administration of d-Amphetamine Results in a Time-dependent and Dose-independent Sustained Increase in Urinary Excretion of p-Hydroxyamphetamine in Mice

Carvalho Felix,Soares Maria Elisa,Fernandes Eduarda [他],Remiao Fernando,Carvalho Marcia,Duarte Jose Alberto,Pires-das-Neves Ricardo,Pereira Maria de Lourdes,Bastos Maria de Lourdes
Journal of health science 53(4), 371-377, 2007-08-01
… The biotransformation of d-amphetamine into p-hydroxyamphetamine (HA) by cytochrome P450 occurs in several species besides humans. … Charles River Caesarian Derived (CD)-1 mice, kept in metabolic cages, were treated with d-amphetamine (5, 10 and 20mg/kg, i.p., daily, for 14days). …
NAID 110006366914

Determination of amphetamine and its metabolite p-hydroxyamphetamine in rat urine by reversed-phase high-performance liquid chromatography after dabsyl derivatization

SOARES M. E.
Biomed. Chromatogr. 15, 452-456, 2001
NAID 30010519277

Simultaneous gas chromatographic determination of methamphetamine, amphetamine and their p-hydroxylated metabolites in plasma and urine

CHEUNG S.,NOLTE H.,OTTON S. V.,TYNDALE R. F.,WU P. H.,SELLERS E. M.
Journal of chromatography. B, Biomedical sciences and applications 690(1), 77-87, 1997-03-07
NAID 10024511986

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リンク元	「パラヒドロキシアンフェタミン」
関連記事	「P」「hydroxyamphetamine」「ps」「p」

「パラヒドロキシアンフェタミン」

4-Hydroxyamphetamine
Systematic (IUPAC) name
	4-(2-aminopropyl)phenol
Clinical data
Trade names	Hydroxyamfetamine, Paredrine
Legal status	℞ (Prescription only);
Routes of; administration	Topical (ocular)
Identifiers
CAS Registry Number	1518-86-1
ATC code	None
PubChem	CID: 3651
ChemSpider	3525
ChEMBL	CHEMBL1546
Chemical data
Formula	C9H13NO
Molecular mass	151.206 g/mol
	SMILES Oc1ccc(cc1)CC(N)C ;
	InChI InChI=1S/C9H13NO/c1-7(10)6-8-2-4-9(11)5-3-8/h2-5,7,11H,6,10H2,1H3 ; Key:GIKNHHRFLCDOEU-UHFFFAOYSA-N ;
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