Effects of inhibitors of neuronal uptake of 5-HT on sympathetic cardiovascular regulation.
The effect on sympathetic cardiovascular regulation of inhibition of the high-affinity neuronal uptake of 5-hydroxytryptamine (5-HT) by fluvoxamine, citalopram, and fluoxetine was studied in anesthetized rabbits. The mean arterial pressure, postganglionic renal sympathetic nerve activity, heart rate, clearance of [3H]norepinephrine from plasma and the plasma norepinephrine concentration were measured, and from the latter two parameters the spillover of norepinephrine into the blood was calculated. The effect of fluvoxamine and fluoxetine on the uptake of [3H]5-HT into platelets was also examined. Of four increasing doses of fluvoxamine (0.6, 1.7, 5, and 15 mg/kg i.v.) and citalopram (0.3, 1, 3, and 9 mg/kg i.v.), only the two highest ones decreased the renal sympathetic nerve activity, heart rate, and clearance of [3H]norepinephrine from plasma. Only the highest of four increasing doses of fluoxetine (0.2, 0.6, 1.7, and 5 mg/kg i.v.) inhibited sympathetic nerve activity. However, lower doses of fluvoxamine (0.6 and 1.7 mg/kg i.v.) and fluoxetine (0.6 and 1.7 mg/kg i.v.) already markedly inhibited the uptake of [3H]5-HT into platelets. The data indicate that selective inhibition of neuronal uptake of 5-HT has no effect on central sympathetic regulation in anesthetized rabbits. The sympathoinhibition observed at high doses of fluvoxamine and citalopram is probably due to inhibition of the neuronal uptake of norepinephrine.
Szabo
B
B
Pharmakologisches Institut, Albert-Ludwigs-Universität, Freiburg, Germany.
Karsch
V
V
Starke
K
K
D000704:Analysis of Variance; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000494:pharmacology*; D016666:Fluvoxamine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D011817:Rabbits; D012701:Serotonin; D013564:Sympathetic Nervous System / Q000187:drug effects*
D005473:Fluoxetine; D015283:Citalopram; D012701:Serotonin; D016666:Fluvoxamine; D009638:Norepinephrine