Effects of the alpha 2-antagonist idazoxan on monoaminergic parameters measured in the cerebrospinal fluid of rabbits.
The alpha 2-antagonist idazoxan was administered intravenously to rabbits. The increase in central noradrenergic, dopaminergic and serotonergic activity was followed as a function of time by determining neuronal parameters in the cerebrospinal fluid (CSF) and was compared with changes previously determined after yohimbine. These parameters include the enzyme dopamine-beta-hydroxylase (D beta H), the noradrenergic metabolites 3-methoxy-4-hydroxyphenylmandelic acid (VMA) and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), the dopaminergic metabolite 3-methoxy-4-hydroxyphenylacetic acid (HVA) and the serotonergic metabolite 5-hydroxyindole acetic acid (5-HIAA). Control experiments with physiological saline were also performed. D beta H activity increased to 211% in control experiments, and to 570 and 530%, respectively after yohimbine and idazoxan. Compared to the control experiments yohimbine was able to elevate VMA, MHPG and HVA concentrations, but 5-HIAA levels were reduced. Idazoxan caused increased MHPG concentrations, slight increases in VMA, little effect on HVA and no effect on 5-HIAA levels. We conclude that idazoxan was as potent as yohimbine as an alpha 2-antagonist in our in vivo experiments and that idazoxan shows a much greater selectivity with regard to the noradrenergic system.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D004299:Dopamine beta-Hydroxylase / Q000134:cerebrospinal fluid*; D005260:Female; D006018:Glycols / Q000134:cerebrospinal fluid*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid*; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid*; D019329:Idazoxan; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid*; D011817:Rabbits; D014642:Vanilmandelic Acid / Q000134:cerebrospinal fluid*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004147:Dioxins; D006018:Glycols; D015016:Yohimbine; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D014642:Vanilmandelic Acid; D004299:Dopamine beta-Hydroxylase; D006719:Homovanillic Acid; D019329:Idazoxan