Browse history interactively

Page 1

Page 1Revision 1

Page 2

Page 2Revision 2

← Previous editContent deleted Content addedVisualWikitext

Revision as of 08:43, 6 August 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,084 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEBI').← Previous edit		Latest revision as of 08:11, 1 September 2024 edit undo76.174.0.57 (talk) Navbox, cat.
(73 intermediate revisions by 26 users not shown)
Line 1:		Line 1:
	{{chembox		{{chembox
	| verifiedrevid = 413110980		| verifiedrevid = 443314408
	|ImageFile=2-Hydroxyphenethylamine.png		| ImageFile =Phenylethanolamine.png
	|ImageSize=200px		| ImageSize =
			| ImageFile2 = (S)-Phenylethanolamine molecule ball.png
⚫	|IUPACName=2-Amino-1-phenylethanol
			| ImageAlt2 = Ball-and-stick model of the phenylethanolamine molecule
⚫	|OtherNames=
		⚫	| IUPACName =2-Amino-1-phenylethanol
		⚫	| OtherNames =
	|Section1={{Chembox Identifiers		|Section1={{Chembox Identifiers
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 975		| ChemSpiderID = 975
	| KEGG_Ref = {{keggcite|correct|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
Line 19:		Line 21:
	| StdInChIKey = ULSIYEODSMZIPX-UHFFFAOYSA-N		| StdInChIKey = ULSIYEODSMZIPX-UHFFFAOYSA-N
	| CASNo_Ref = {{cascite|correct|CAS}}		| CASNo_Ref = {{cascite|correct|CAS}}
	| CASNo=7568-93-6		| CASNo =7568-93-6
			| UNII_Ref = {{fdacite|correct|FDA}}
	| PubChem=1000
	| ChEBI = 16343		| UNII = 2P4Y56479O
			| PubChem =1000
			| ChEBI_Ref = {{ebicite|correct|EBI}}
			| ChEBI = 16343
	| SMILES = OC(c1ccccc1)CN		| SMILES = OC(c1ccccc1)CN
	}}		}}
	|Section2={{Chembox Properties		|Section2={{Chembox Properties
	| Formula=C<sub>8</sub>H<sub>11</sub>NO		| Formula =C<sub>8</sub>H<sub>11</sub>NO
	| MolarMass=137.18 g/mol		| MolarMass =137.18 g/mol
	| Appearance=		| Appearance =pale yellow solid
	| Density=		| Density =
			| MeltingPtC = 56 to 57
	| MeltingPt=
			| MeltingPt_notes =
	| BoilingPt=
			| BoilingPtC = 157 to 160
	| Solubility=
			| BoilingPt_notes = at 17 mmHg
			| Solubility =soluble
	}}		}}
	|Section3={{Chembox Hazards		|Section3={{Chembox Hazards
	| MainHazards=		| MainHazards =
	| FlashPt=		| FlashPt =
			| AutoignitionPt =
	| Autoignition=
	}}		}}
	}}		}}
			'''Phenylethanolamine''' (sometimes abbreviated '''PEOH'''), or '''β-hydroxyphenethylamine''', is a ] with a structure similar to those of other ] as well as the ] ], ], and ]. As an ], phenylethanolamine is a β-hydroxylated ] that is also structurally related to a number of synthetic drugs in the ] class. In common with these compounds, phenylethanolamine has strong ] activity<ref>W. H. Hartung (1945). "Beta-phenethylamine derivatives." ''Ind. Eng. Chem.'' '''37''' 126–136.</ref> and, under the name ''Apophedrin'', has been used as a drug to produce topical ].<ref name = Mer>''The Merck Index, 10th Ed.'' (1983), p. 1051, Merck & Co., Rahway.</ref>
	'''2-Hydroxyphenethylamine''' ('''2-OH-PEA''') is an ].
			In appearance, phenylethanolamine is a white solid.
	{{organic-compound-stub}}
			Phenylethanolamine is perhaps best known in the field of bioscience as part of the ] name "]", referring to an enzyme which is responsible for the conversion of ] into ], as well as other related transformations.<ref>J. Axelrod (1966). "Methylation reactions in the formation and metabolism of catecholamines and other biogenic amines. ''Pharmacol. Rev.'' '''18''' 95–113.</ref>
⚫	== References ==
	{{Unreferenced|date=August 2009}}
⚫	{{Reflist|2}}
			==Occurrence==
			Phenylethanolamine has been found to occur naturally in several animal species, including humans.<ref>E. E. Inwang, A. D. Mosnaim and H. C. Sabelli (1973). "Isolation and characterization of phenethylamine and phenylethanolamine from human brain." ''J. Neurochem.'' '''20''' 1469–1473.</ref><ref>H. E. Shannon and C. M. Degregorio (1982). "Self-administration of the endogenous trace amines beta-phenylethylamine, N-methyl phenylethylamine and phenylethanolamine in dogs." ''J. Pharmacol. Exp. Ther.'' '''222''' 52–60.</ref>
			==Chemistry==
⚫	{{Phenethylamines}}
			===Synthesis===
⚫	]
			An early synthesis of phenylethanolamine was by the reduction of 2-nitro-1-phenyl-ethanol.<ref name = All>G. A. Alles (1927). "The comparative physiological action of phenylethanolamine." ''J. Pharmacol. Exp. Ther.'' '''32''' 121–133.</ref> Other early syntheses are summarized in a paper by Hartung and Munch.<ref>W. H. Hartung and J. C. Munch (1929). "Amino alcohols. I. Phenylpropanolamine and para-tolylpropanolamine." ''J. Am. Chem. Soc.'' '''51''' 2262–2266.</ref>
			A more recent synthesis, providing a better yield, is by the reduction of ] using ].<ref>A. Burger and E. D. Hornbacker (1952). "Reduction of acyl cyanides with lithium aluminum hydride." ''J. Am. Chem. Soc.'' '''74''' 5514.</ref>
			===Properties===
			Chemically, phenyethanolamine is an ] compound, an ], and an alcohol. The amino-group makes this compound a ], capable of reacting with acids to form salts.
			Two common salts of phenylethanolamine are the hydrochloride, C<sub>8</sub>H<sub>11</sub>NO.HCl, m.p.&nbsp;212&nbsp;°C,<ref name = All/> and the sulfate, (C<sub>8</sub>H<sub>11</sub>NO)<sub>2</sub>.H<sub>2</sub>SO<sub>4</sub>, m.p.&nbsp;239–240&nbsp;°C.<ref name = Mer/><ref name = Tain>M. L. Tainter (1929). "Pharmacological actions of phenylethanolamine." ''J. Pharmacol. Exp. Ther.'' '''36''' 29–54.</ref>
			The '''pK<sub>a</sub>''' of phenylethanolamine hydrochloride, at 25&nbsp;°C and at a concentration of 10mM, has been recorded as 8.90.<ref>J. Armstrong and R. B. Barlow (1976). "The ionization of phenolic amines, including apomorphine, dopamine and catecholamines and an assessment of zwitterion constants." ''Br. J. Pharmacol.'' '''57''' 501–516.</ref>
			The presence of the hydroxy-group on the ] carbon of the phenylethanolamine molecule creates a ], so the compound exists in the form of two ], d- and l-phenylethanolamine, or as the ], d,l-phenylethanolamine. The ] isomer<ref>CAS # 56613-81-1</ref> corresponds to the ], and the levorotatory isomer<ref>CAS # 2549-14-6</ref> to the ]<ref name = Raf>M. F. Rafferty , D. S. Wilson , J. A. Monn , P. Krass , R. T. Borchardt , and G. L. Grunewald (1982). "Importance of the aromatic ring in adrenergic amines. 7. Comparison of the stereoselectivity of norepinephrine N-methyltransferase for aromatics. Nonaromatic substrates and inhibitors." ''J. Med. Chem.'' '''25''' 1198–1204.</ref> The data given at right is for the ].
			The synthesis of (''S'')-(+)-phenylethanolamine, from (+)-], via (+)-], has been described.<ref>A. I. Meyers and J. Slade (1980). "Asymmetric addition of organometallics to chiral ketooxazolines. Preparation of enantiomerically enriched α-hydroxy acids." ''J. Org. Chem.'' '''45''' 2785–2791.</ref> The physical constants reported in this paper are as follows: m.p.&nbsp;55–57&nbsp;°C; = + 47.9° (c 2.4, in ethanol).
			==Pharmacology==
			Early, classical pharmacological studies of phenylethanolamine were carried out by Tainter, who observed its effects after administering it to rabbits, cats and dogs. The drug produced a rapid rise in blood pressure when administered intravenously, but had little or no effect when given by any other route: doses as high as 200&nbsp;mg given ] to rabbits did not alter blood pressure, nor were there any effects when the drug was intubated into the stomach.
			In man, a total oral dose of 1 g also produced no effects.
			Doses of 1–5&nbsp;mg/kg, intravenously, caused no definite changes in respiration in cats or rabbits, and additional experiments showed that phenylethanolamine had no ] properties in animals. There was a similar lack of effect when the drug was given subcutaneously to man.
			''In vivo'' and ''in vitro'' experiments involving cat and rabbit intestinal smooth muscle showed that the drug produced relaxation and inhibition.
			A detailed examination of the ] effect of phenylethanolamine led Tainter to conclude that this drug acted by direct stimulation of the radial dilator muscle in the eye.<ref name = Tain/>
			Shannon and co-workers confirmed and extended some of Tainter's studies. After administering phenylethanolamine to dogs intravenously, these investigators observed that 10–30&nbsp;mg/kg of the drug increased pupil diameter, and decreased body temperature; a dose of 10 or 17.5&nbsp;mg/kg decreased heart rate, but a 30&nbsp;mg/kg dose caused it to increase. Other effects that were noted included profuse salivation and ]. Phenylethanolamine also produced behavioral effects such as stereotyped head movement, rapid eye movement, and repetitive tongue extrusion. These and other observations were suggested to be consistent with an action on α- and β-adrenergic receptors.<ref name = Shan>H. E. Shannon, E. J. Cone and D. Yousefnejad (1981). "Physiologic effects and plasma kinetics of phenylethanolamine and its N-methyl homolog in the dog." ''J. Pharmacol. Exp. Ther.'' '''217''' 379–385.</ref>
			Research by Carpéné and co-workers showed that phenylethanolamine<ref>The drug was tested in the form of a ] mixture.</ref> did not significantly stimulate ] in cultured ] ("fat cells") from guinea pig or human. Moderate stimulation (] about half that of the reference standard, ]) was observed in adipocytes from rat or hamster. This lipolysis was inhibited completely by ] (considered to be a non-selective ]), ] (considered to be a selective β<sub>1</sub>-antagonist), and ] (considered to be a selective β<sub>2</sub>-antagonist), but not by ] (considered to be a selective β<sub>3</sub>-antagonist).<ref>C. Carpéné, J. Galitzky, E. Fontana, C. Atgié, M. Lafontan and M. Berlan(1999). "Selective activation of β<sub>3</sub>- adrenoceptors by octopamine: comparative studies in mammalian fat cells." ''Naunyn-Schmiedebergs Arch. Pharmacol.'' '''359''' 310–321.</ref>
			Using a β<sub>2</sub> ] preparation derived from ] ] cells, Liappakis and co-workers<ref>G. Liapakis, W. C. Chan, M. Papadokostaki and J. A. Javitch (2004). "Synergistic contributions of the functional groups of epinephrine to its affinity and efficacy at the β<sub>2</sub> adrenergic receptor." ''Mol. Pharmacol.'' '''65''' 1181–1190.</ref> found that in ] receptors, racemic phenylethanolamine<ref>Named imprecisely as "hydroxyphenethylamine"</ref> had ~ 1/400 x the affinity of epinephrine, and ~ 1/7 x the affinity of norepinephrine in competition experiments with <sup>3</sup>-].<ref>Considered to be an antagonist of β<sub>1</sub> and β<sub>2</sub> receptors, and an agonist of β<sub>3</sub> receptors.</ref>
			The two enantiomers of phenylethanolamine were studied for their interaction with the human trace amine associated receptor (]) by a research group at ]. From experiments with human TAAR1 expressed in rGα<sub>s</sub>AV12-664 cells, Wainscott and co-workers observed that R-(−)-phenylethanolamine (referred to as "R-(−)-β-hydroxy-β-phenylethylamine") had an ED<sub>50</sub> of ~1800 nM, with an E<sub>max</sub> of ~ 110%, whereas S-(+)-phenylethanolamine (referred to as "S-(+)-β-hydroxy-β-phenylethylamine") had an ED<sub>50</sub> of ~1720 nM, with an E<sub>max</sub> of ~ 105%. In comparison, ] itself had an ED<sub>50</sub> of ~106 nM, with an E<sub>max</sub> of ~ 100%.<ref name="TAAR1 ligands">{{cite journal |vauthors=Wainscott DB, Little SP, Yin T, Tu Y, Rocco VP, He JX, Nelson DL |title=Pharmacologic characterization of the cloned human trace amine-associated receptor1 (TAAR1) and evidence for species differences with the rat TAAR1 |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=320 |issue=1 |pages=475–485 |date=January 2007 |pmid=17038507 |doi=10.1124/jpet.106.112532 |s2cid=10829497 | quote = Substitution on the ethylamine side chain produced a variety of effects on potency at the human TAAR1, depending on the nature of the substituent. For example, a β-methyl substituent was well tolerated, being as potent as β-PEA itself (Table 3). However, changing that substitution to a β-hydroxy resulted in a 10-fold reduction in potency&nbsp;...|url=http://pdfs.semanticscholar.org/91d4/65d751e4e6d6ba083daa6f4069ecc4f9ae6c.pdf |archive-url=https://web.archive.org/web/20190227151431/http://pdfs.semanticscholar.org/91d4/65d751e4e6d6ba083daa6f4069ecc4f9ae6c.pdf |url-status=dead |archive-date=2019-02-27 }}<br />""</ref> In other words, phenylethanolamine is a ] and ].<ref name="TAAR1 ligands" />
			==Pharmacokinetics==
			The pharmacokinetics of phenylethanolamine, after intravenous administration to dogs, were studied by Shannon and co-workers, who found that the drug followed the "two-compartment model", with T<sub>1/2</sub>(α) ≃ 6.8 mins and T<sub>1/2</sub>(β) ≃ 34.2 mins; the "plasma half-life" of phenylethanolamine was therefore about 30 minutes.<ref name = Shan/>
			==Biochemistry==
			Phenylethanolamine was found to be an excellent substrate for the ] ] (PNMT), first isolated from monkey ] by ], which transformed it into N-methylphenylethanolamine.<ref>J.Axelrod (1962). "Purification and properties of phenylethanolamine-N-methyl transferase." ''J. Biol. Chem.'' '''237''' 1657–1660.</ref>
			Subsequent studies by Rafferty and co-workers showed that substrate specificity of PNMT from bovine adrenal glands for the different ] of phenylethanolamine was in the order R-(−)-PEOH > R,S-(racemic)-PEOH > S-(+)-PEOH.<ref name = Raf/>
			==Toxicology==
			The minimum lethal dose (m.l.d.) upon subcutaneous administration to guinea pigs was ~ 1000&nbsp;mg/kg; the m.l.d. upon intravenous administration to rabbits was 25–30&nbsp;mg/kg.;<ref name = All/> in rats, the m.l.d. after intravenous administration was 140&nbsp;mg/kg.<ref name = Tain/>
			==See also==
			* ]
			* ]
		⚫	==References==
		⚫	{{Reflist}}
			==External links==
			*{{Commonscatinline|Phenylethanolamines}}
			{{TAAR ligands|state=expanded}}
			{{Adrenergic receptor modulators}}
			{{Monoamine releasing agents}}
		⚫	{{Phenethylamines}}
			]
	{{DEFAULTSORT:Hydroxyphenethylamine, 2-}}
			]
		⚫	]
			]
			]