Abstract
The effect of reboxetine on sympathetic neuroeffector transmission in rabbit isolated carotid artery was examined. Reboxetine (10-8-3 × 10-6 M) and cocaine (10-6-3 × 10-5 M), but not desipramine (10-8-3 × 10-7 M), increased contractions evoked by electrical field stimulation. At higher concentrations, reboxetine (10-4 M), cocaine (3 × 10-4 M), and desipramine (3 × 10-7-10-5 M) inhibited the neurogenic contractions. The enhancement seen with reboxetine and cocaine was partially reversible, whereas the inhibition was readily reversible. Reboxetine (10-7 M) and cocaine (10-5 M) prevented the inhibitory action of bretylium (10-6 M). Reboxetine (10-8-10-5 M), desipramine (10-7-10-4 M), and cocaine (10-6-10-5 M) increased the stimulation-evoked [3H]norepinephrine release. Pargyline (5 × 10-4 M) augmented the facilitatory effect of reboxetine (3 × 10-9-10-6 M) and cocaine (10-7-3 × 10-5 M). Reboxetine (10-8-10-6 M), desipramine (10-8-10-6 M), and cocaine (3 × 10-8-10-5 M) reduced the [3H]norepinephrine (10-8 M) uptake. Reboxetine (10-7 M) and cocaine (10-5-2 × 10-4 M) enhanced the contractions evoked by phenylephrine and norepinephrine. Higher concentrations of reboxetine antagonized the contractions. Reboxetine (10-5-6 × 10-5 M) antagonized the contractions evoked by potassium. The contractions evoked by tyramine (3 × 10-6-10-3 M) was reduced by reboxetine (3 × 10-8-10-6 M) and by cocaine (10-7-10-5 M). We conclude that reboxetine inhibits the membrane amine pump (uptake-1) in the terminals of postganglionic adrenergic neurons in a cocaine-like manner.
Footnotes
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This study was supported by a grant from the Danish Medical Research Council.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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DOI: 10.1124/jpet.103.052233.
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ABBREVIATIONS: NET, norepinephrine transporter; U-0521, 1-(3,4-dihydroxyphenyl)-2-methyl-1-propanone; PSS, physiological salt solution; MAO, monoamine oxidase; ANOVA, analysis of variance.
- Received March 28, 2003.
- Accepted May 8, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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