Phenylethanolamine (sometimes abbreviated PEOH), or β-hydroxyphenethylamine, is a trace amine with a structure similar to those of other trace phenethylamines as well as the catecholamine neurotransmitters dopamine, norepinephrine, and epinephrine. As an organic compound, phenylethanolamine is a β-hydroxylated phenethylamine that is also structurally related to a number of synthetic drugs in the substituted phenethylamine class. In common with these compounds, phenylethanolamine has strong cardiovascular activity and, under the name Apophedrin, has been used as a drug to produce topical vasoconstriction.
In appearance, phenylethanolamine is a white solid.
Phenylethanolamine is perhaps best known in the field of bioscience as part of the enzyme name "phenylethanolamine N-methyl transferase", referring to an enzyme which is responsible for the conversion of norepinephrine into epinephrine, as well as other related transformations.
Occurrence
Phenylethanolamine has been found to occur naturally in several animal species, including humans.
Chemistry
Synthesis
An early synthesis of phenylethanolamine was by the reduction of 2-nitro-1-phenyl-ethanol. Other early syntheses are summarized in a paper by Hartung and Munch.
A more recent synthesis, providing a better yield, is by the reduction of benzoyl cyanide using LiAlH4.
Properties
Chemically, phenyethanolamine is an aromatic compound, an amine, and an alcohol. The amino-group makes this compound a weak base, capable of reacting with acids to form salts.
Two common salts of phenylethanolamine are the hydrochloride, C8H11NO.HCl, m.p. 212 °C, and the sulfate, (C8H11NO)2.H2SO4, m.p. 239–240 °C.
The pKa of phenylethanolamine hydrochloride, at 25 °C and at a concentration of 10mM, has been recorded as 8.90.
The presence of the hydroxy-group on the benzylic carbon of the phenylethanolamine molecule creates a chiral center, so the compound exists in the form of two enantiomers, d- and l-phenylethanolamine, or as the racemic mixture, d,l-phenylethanolamine. The dextrorotatory isomer corresponds to the S-configuration, and the levorotatory isomer to the R-configuration The data given at right is for the racemate.
The synthesis of (S)-(+)-phenylethanolamine, from (+)-mandelic acid, via (+)-mandelamide, has been described. 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 subcutaneously 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 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 mydriatic effect of phenylethanolamine led Tainter to conclude that this drug acted by direct stimulation of the radial dilator muscle in the eye.
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 piloerection. 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.