Effects of pyrroxan and chlordiazepoxide on biogenic amine metabolism in the rat brain.
Pyrroxan (20 mg/kg, i.p.), a new potential antianxiety agent, increased brain norepinephrine (NE) turnover in rats, reflecting a possible central alpha-adrenergic receptor blocking activity. In contrast, chlordiazepoxide (20 mg/kg, i.p.), a widely used antianxiety agent, did not alter the NE turnover. Pyrroxan did not affect overall DA turnover although it did appear to accelerate DA turnover initially. The initial potentiation of DA turnover may indicate a short-lasting blocking action on DA receptors. In comparison, chlordiazepoxide (20 mg/kg, i.p.) decreased the turnover rate of DA. Effects of both drugs on 5-HT indicate a decrease in turnover with no significant monoamine oxidase activity or blockade of the 5-HT reuptake mechanism. Both drugs antagonized the decline in intraventicularly-injected 14C-5-HT. Neither drug caused consistent changes in endogenous 5-HT, 5-hydroxyindoleacetic acid, or tryptophan levels. Neither drug potentiated the behavioral effects of L-Dopa nor increased the 5-HTP behavoiral syndrome in the mouse. Pyrroxan may be expected to exhibit a spectrum of activity between that of minor and major tranquilizers, characterized by antianxiety action together with sedative or tranquilizing activity.
D000818:Animals; D014151:Anti-Anxiety Agents; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002707:Chlordiazepoxide / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D008996:Monoamine Oxidase Inhibitors; D009638:Norepinephrine / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism
D014151:Anti-Anxiety Agents; D001679:Biogenic Amines; D004146:Dioxanes; D004147:Dioxins; D008781:Methyltyrosines; D008996:Monoamine Oxidase Inhibitors; D011759:Pyrrolidines; D012701:Serotonin; D002707:Chlordiazepoxide; D004298:Dopamine; D009638:Norepinephrine