Phenylethanolamine
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IUPAC name
2-Amino-1-phenylethanol
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Identifiers | |
3D model (
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ChEBI | |
ChEMBL | |
ChemSpider | |
ECHA InfoCard
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100.028.609 |
KEGG | |
PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
C8H11NO | |
Molar mass | 137.18 g/mol |
Appearance | pale yellow solid |
Melting point | 56 to 57 °C (133 to 135 °F; 329 to 330 K) |
Boiling point | 157 to 160 °C (315 to 320 °F; 430 to 433 K) at 17 mmHg |
soluble | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Phenylethanolamine (sometimes abbreviated PEOH), or β-hydroxyphenethylamine, is a
In appearance, phenylethanolamine is a white solid.
Phenylethanolamine is perhaps best known in the field of bioscience as part of the
Occurrence
Phenylethanolamine has been found to occur naturally in several animal species, including humans.[4][5]
Chemistry
Synthesis
An early synthesis of phenylethanolamine was by the reduction of 2-nitro-1-phenyl-ethanol.[6] Other early syntheses are summarized in a paper by Hartung and Munch.[7]
A more recent synthesis, providing a better yield, is by the reduction of benzoyl cyanide using LiAlH4.[8]
Properties
Chemically, phenyethanolamine is an
, capable of reacting with acids to form salts.Two common salts of phenylethanolamine are the hydrochloride, C8H11NO.HCl, m.p. 212 °C,[6] and the sulfate, (C8H11NO)2.H2SO4, m.p. 239–240 °C.[2][9]
The pKa of phenylethanolamine hydrochloride, at 25 °C and at a concentration of 10mM, has been recorded as 8.90.[10]
The presence of the hydroxy-group on the
The synthesis of (S)-(+)-phenylethanolamine, from (+)-mandelic acid, via (+)-mandelamide, has been described.[14] The physical constants reported in this paper are as follows: m.p. 55–57 °C; [α] = + 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 mg given
In man, a total oral dose of 1 g also produced no effects.
Doses of 1–5 mg/kg, intravenously, caused no definite changes in respiration in cats or rabbits, and additional experiments showed that phenylethanolamine had no broncho-dilatory 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
Shannon and co-workers confirmed and extended some of Tainter's studies. After administering phenylethanolamine to dogs intravenously, these investigators observed that 10–30 mg/kg of the drug increased pupil diameter, and decreased body temperature; a dose of 10 or 17.5 mg/kg decreased heart rate, but a 30 mg/kg dose caused it to increase. Other effects that were noted included profuse salivation and
Research by Carpéné and co-workers showed that phenylethanolamine
Using a β2
The two enantiomers of phenylethanolamine were studied for their interaction with the human trace amine associated receptor (
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 T1/2(α) ≃ 6.8 mins and T1/2(β) ≃ 34.2 mins; the "plasma half-life" of phenylethanolamine was therefore about 30 minutes.[15]
Biochemistry
Phenylethanolamine was found to be an excellent substrate for the
Subsequent studies by Rafferty and co-workers showed that substrate specificity of PNMT from bovine adrenal glands for the different
Toxicology
The minimum lethal dose (m.l.d.) upon subcutaneous administration to guinea pigs was ~ 1000 mg/kg; the m.l.d. upon intravenous administration to rabbits was 25–30 mg/kg.;[6] in rats, the m.l.d. after intravenous administration was 140 mg/kg.[9]
See also
References
- ^ W. H. Hartung (1945). "Beta-phenethylamine derivatives." Ind. Eng. Chem. 37 126–136.
- ^ a b The Merck Index, 10th Ed. (1983), p. 1051, Merck & Co., Rahway.
- ^ J. Axelrod (1966). "Methylation reactions in the formation and metabolism of catecholamines and other biogenic amines. Pharmacol. Rev. 18 95–113.
- ^ 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.
- ^ 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.
- ^ a b c G. A. Alles (1927). "The comparative physiological action of phenylethanolamine." J. Pharmacol. Exp. Ther. 32 121–133.
- ^ W. H. Hartung and J. C. Munch (1929). "Amino alcohols. I. Phenylpropanolamine and para-tolylpropanolamine." J. Am. Chem. Soc. 51 2262–2266.
- ^ A. Burger and E. D. Hornbacker (1952). "Reduction of acyl cyanides with lithium aluminum hydride." J. Am. Chem. Soc. 74 5514.
- ^ a b c M. L. Tainter (1929). "Pharmacological actions of phenylethanolamine." J. Pharmacol. Exp. Ther. 36 29–54.
- ^ 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.
- ^ CAS # 56613-81-1
- ^ CAS # 2549-14-6
- ^ a b 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.
- ^ 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.
- ^ a b 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.
- racemicmixture.
- ^ C. Carpéné, J. Galitzky, E. Fontana, C. Atgié, M. Lafontan and M. Berlan(1999). "Selective activation of β3- adrenoceptors by octopamine: comparative studies in mammalian fat cells." Naunyn-Schmiedebergs Arch. Pharmacol. 359 310–321.
- ^ 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 β2 adrenergic receptor." Mol. Pharmacol. 65 1181–1190.
- ^ Named imprecisely as "hydroxyphenethylamine"
- ^ Considered to be an antagonist of β1 and β2 receptors, and an agonist of β3 receptors.
- ^ S2CID 10829497. Archived from the original (PDF) on 2019-02-27."
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 ...
"Table 3 - ^ J.Axelrod (1962). "Purification and properties of phenylethanolamine-N-methyl transferase." J. Biol. Chem. 237 1657–1660.
External links
- Media related to Phenylethanolamines at Wikimedia Commons