Effects of dl-norephedrine and its enantiomers on norepinephrine uptake and release in isolated rat caudal artery.
Racemic norephedrine (dl-NOR), is a phenylethylamine derivative that is pharmacologically classified as a mixed-acting sympathomimetic amine. It is the active ingredient in many over-the-counter nasal decongestants and diet aid products. This research project was performed to examine the effects of dl-NOR and constituent enantiomers on the uptake and release of tritiated norepinephrine (3H-NE) in vascular tissue. All three NOR species significantly inhibited the uptake of 3H-NE into the isolated caudal artery of male Sprague-Dawley rats (p < 0.01). There was no significant difference in potency between either d- or l-NOR for this effect. There was, however, no effect of any NOR species on 3H-NE release, not even at concentrations which effectively inhibited uptake. These results indicate that inhibition of NE reuptake may be a component of the mechanism of action of NOR, but that a displacement of NE from neuronal storage sites is not. However, because the vasoactive effects of NOR have been shown to be mediated almost exclusively through the l-enantiomer, the lack of stereoselectivity in the current study indicates that the blockade of NE uptake by NOR is only a minor component of its vasoactive properties.
Hricik
J G
JG
Department of Pharmacology-Toxicology, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
Johnson
D A
DA
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000294:innervation* / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D009638:Norepinephrine / Q000493:pharmacokinetics*; D010665:Phenylpropanolamine / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D013566:Sympathomimetics / Q000737:chemistry / Q000494:pharmacology*; D013623:Tail / Q000098:blood supply; D014316:Tritium; D014439:Tyramine / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D018377:Neurotransmitter Agents; D013566:Sympathomimetics; D014316:Tritium; D010665:Phenylpropanolamine; D003891:Desipramine; D009638:Norepinephrine; D014439:Tyramine