PT - JOURNAL ARTICLE AU - Lasse E. Rasmussen AU - Ove A. Nedergaard TI - Effects of Reboxetine on Sympathetic Neuroeffector Transmission in Rabbit Carotid Artery AID - 10.1124/jpet.103.052233 DP - 2003 Sep 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 995--1002 VI - 306 IP - 3 4099 - http://jpet.aspetjournals.org/content/306/3/995.short 4100 - http://jpet.aspetjournals.org/content/306/3/995.full SO - J Pharmacol Exp Ther2003 Sep 01; 306 AB - 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. The American Society for Pharmacology and Experimental Therapeutics