Effects of reboxetine on sympathetic neuroeffector transmission in rabbit carotid artery.
The effect of reboxetine on sympathetic neuroeffector transmission in rabbit isolated carotid artery was examined. Reboxetine (10-8-3 x 10-6 M) and cocaine (10-6-3 x 10-5 M), but not desipramine (10-8-3 x 10-7 M), increased contractions evoked by electrical field stimulation. At higher concentrations, reboxetine (10-4 M), cocaine (3 x 10-4 M), and desipramine (3 x 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 x 10-4 M) augmented the facilitatory effect of reboxetine (3 x 10-9-10-6 M) and cocaine (10-7-3 x 10-5 M). Reboxetine (10-8-10-6 M), desipramine (10-8-10-6 M), and cocaine (3 x 10-8-10-5 M) reduced the [3H]norepinephrine (10-8 M) uptake. Reboxetine (10-7 M) and cocaine (10-5-2 x 10-4 M) enhanced the contractions evoked by phenylephrine and norepinephrine. Higher concentrations of reboxetine antagonized the contractions. Reboxetine (10-5-6 x 10-5 M) antagonized the contractions evoked by potassium. The contractions evoked by tyramine (3 x 10-6-10-3 M) was reduced by reboxetine (3 x 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.
Rasmussen
Lasse E
LE
Department of Pharmacology, University of Southern Denmark, Odense, Denmark.
Nedergaard
Ove A
OA
D000818:Animals; D001949:Bretylium Compounds / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology*; D009451:Neuroeffector Junction / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D000077593:Reboxetine; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014316:Tritium
D001949:Bretylium Compounds; D009025:Morpholines; D014316:Tritium; D000077593:Reboxetine; D010293:Pargyline; D003042:Cocaine; D011188:Potassium; C045166:bretylium; D003891:Desipramine; D009638:Norepinephrine