title: Thyrotropin-releasing hormone selectively reverses lorazepam-induced sedation but not slowing of saccadic eye movements.
abstract: To investigate preliminary reports that benzodiazepine-induced sedation may be reversed by thyrotropin-releasing hormone (TRH), we examined the effect of TRH or saline placebo on two variables which are sensitive to benzodiazepine agonists: changes in sedation and saccadic eye movements. Lorazepam 10 micrograms/kg i.v. increased self-ratings of sedation and reduced self-ratings of alertness and these changes were almost completely reversed by TRH. In contrast the slowing of saccadic eye movements by lorazepam was not reversed by TRH. The effects of TRH do not appear to be due to a direct antagonism at the benzodiazepine receptor, since flumazenil reverses changes in both variables. Moreover ligand binding studies reveal that TRH has very low affinity at this receptor. These clinical data provide the first demonstration that it is possible to distinguish between the effects of benzodiazepines on saccadic eye movements and psychological self-ratings.
authors.affiliation: Reckitt and Colman Psychopharmacology Unit, School of Medical Sciences, University Walk, Bristol, UK.
authors.forename: P
authors.initials: P
authors.lastname: Glue
authors.forename: J
authors.initials: J
authors.lastname: Bailey
authors.forename: S
authors.initials: S
authors.lastname: Wilson
authors.forename: A
authors.initials: A
authors.lastname: Hudson
authors.forename: D J
authors.initials: DJ
authors.lastname: Nutt
mesh_terms: D000328:Adult; D016292:Procedural Sedation; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008140:Lorazepam / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000378:metabolism; D012438:Saccades / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D011963:Receptors, GABA-A; D005442:Flumazenil; D013973:Thyrotropin-Releasing Hormone; D005445:Flunitrazepam; D008140:Lorazepam