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 i.v., but had little or no effect when given by any other route: doses as high as 200 mg given s.c. 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, i.v., 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 s.c. 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.
Research by Carpéné and co-workers showed that phenylethanolamine did not significantly stimulate lipolysis in cultured adipocytes ("fat cells") from guinea pig or human. Moderate stimulation (intrinsic activities about half that of the reference standard, isoprenaline) was observed in adipocytes from rat or hamster. This lipolysis was inhibited completely by bupranolol (considered to be a non-selective β-blocker), CGP 20712A (considered to be a selective β1-antagonist), and ICI 118,551 (considered to be a selective β2-antagonist), but not by SR 59230A (considered to be a selective β3-antagonist).
Using a β2 adrenergic receptor preparation derived from transfected HEK 293 cells, Liappakis and co-workersfound that in wild-type receptors, racemic phenylethanolamine had ~ 1/400 x the affinity of epinephrine, and ~ 1/7 x the affinity of norepinephrine in competition experiments with 3-CGP-12177.
The two enantiomers of phenylethanolamine were studied for their interaction with the human trace amine receptor (TAAR1) by a research group at Eli Lilly. From experiments with human TAAR1 expressed in rGαsAV12-664 cells, Wainscott and co-workers observed that R-(-)-phenylethanolamine (referred to as "R-(-)-β-hydroxy-β-phenylethylamine") had an ED50 of ~1800 nM, with an Emax of ~ 110%, whereas S-(+)-phenylethanolamine (referred to as "S-(+)-β-hydroxy-β-phenylethylamine") had an ED50 of ~1720 nM, with an Emax of ~ 105%. In comparison, β-phenethylamine itself had an ED50 of ~106 nM, with an Emax of ~ 100%.
Read more about this topic: 2-Hydroxyphenethylamine