In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates.
Article Details
- CitationCopy to clipboard
Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, Birkes J, Young R, Glennon RA
In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates.
J Pharmacol Exp Ther. 2003 Oct;307(1):138-45. Epub 2003 Sep 3.
- PubMed ID
- 12954796 [ View in PubMed]
- Abstract
Ephedrine is a long-studied stimulant available both as a prescription and over-the-counter medication, as well as an ingredient in widely marketed herbal preparations, and is also used as a precursor for the illicit synthesis of methamphetamine. Ephedrine is related to phenylpropanolamine, a decongestant removed from the market place due to concerns that its use increased the risk of hemorrhagic stroke. Standard pharmacology texts emphasize that ephedrine is both a direct and indirect adrenergic agonist, activating adrenergic receptors both by direct agonist activity as well as by releasing norepinephrine via a carrier-mediated exchange mechanism. Chemically, ephedrine possesses two chiral centers. In the present study, we characterized the stereoisomers of ephedrine and the closely related compounds pseudoephedrine, norephedrine, pseudonorephedrine (cathine), methcathinone, and cathinone at biogenic amine transporters and a large battery of cloned human receptors (e.g., "receptorome"). The most potent actions of ephedrine-type compounds were as substrates of the norepinephrine transporter (EC50 values of about 50 nM) followed by substrate activity at the dopamine transporter. Screening the receptorome demonstrated weak affinity at alpha2-adrenergic and 5-hydroxytryptamine7 receptors (Ki values 1-10 microM) and no significant activity at beta-adrenergic or alpha1-adrenergic receptors. Viewed collectively, these data indicate that the pharmacological effects of ephedrine-like phenylpropanolamines are likely mediated by norepinephrine release, and although sharing mechanistic similarities with, they differ in important respects from those of the phenylpropanonamines methcathinone and cathinone and the phenyisopropylamines methamphetamine and amphetamine.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Amphetamine Sodium-dependent noradrenaline transporter Protein Humans UnknownAgonistSubstrateDetails Ephedra sinica root Alpha-2A adrenergic receptor Protein Humans YesAgonistDetails Ephedra sinica root Alpha-2B adrenergic receptor Protein Humans YesAgonistDetails Ephedra sinica root Alpha-2C adrenergic receptor Protein Humans YesAgonistDetails Ephedra sinica root Sodium-dependent dopamine transporter Protein Humans YesNegative modulatorDetails Ephedra sinica root Sodium-dependent noradrenaline transporter Protein Humans YesNegative modulatorDetails - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Amphetamine Sodium-dependent dopamine transporter Ki (nM) 24.8 N/A N/A Details Amphetamine Sodium-dependent noradrenaline transporter Ki (nM) 7.1 N/A N/A Details Oxymetazoline Alpha-2A adrenergic receptor Ki (nM) 1.36 N/A N/A Details Prazosin Alpha-2B adrenergic receptor Ki (nM) 14.6 N/A N/A Details