A comparison between chlordiazepoxide and CL 218,872, a synthetic non-benzodiazepine ligand for benzodiazepine receptors, on serotonin and catecholamine turnover in brain.
Serotonin (5-HT) and catecholamine (CA) turnover rates in midbrain-hindbrain were investigated in rats treated with the benzodiazepine chlordiazepoxide (CDP) or with the anxiolytic triazolopyridazine CL 218,872. A single injection of CDP (2.5-20 mg/kg) decreased 5-HT but not CA turnover rates. Seven daily CDP injections decreased the turnover rates of both 5-HT and CA. In contrast, neither acute nor chronic administration of CL 218,872 (2.5-20 mg/kg) altered baseline turnover rates of 5-HT or CA. Since CL 218,872 has a selective affinity for Type I benzodiazepine receptors, these results suggest that stimulation of Type I receptors is not sufficient to decrease 5-HT or CA turnover rates in midbrain-hindbrain. More importantly, these results question the long-held belief that benzodiazepines exert their anxiolytic and depressant effects through reductions in 5-HT and CA turnover respectively.
McElroy
J F
JF
Feldman
R S
RS
Meyer
J S
JS
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001711:Biotransformation; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002707:Chlordiazepoxide / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D002395:Catecholamines; D006834:Hydrazines; D011724:Pyridazines; D011963:Receptors, GABA-A; D012701:Serotonin; D004295:Dihydroxyphenylalanine; C021604:CL 218872; D002707:Chlordiazepoxide; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan