title: Kindling and withdrawal changes at the benzodiazepine receptor.
abstract: Drugs acting at benzodiazepine receptors can have two types of pharmacological profile: benzodiazepine agonists are anxiolytic, anticonvulsant and sedative, whilst benzo diazepine inverse agonists cause anxiety and convulsions. In 1982 we showed that a benzo diazepine antagonist, Ro 15-1788, prevented the effects of both types of compound at doses without intrinsic activity in the tests used. We put forward the hypothesis that the benzo diazepine receptor complex could undergo two possible conformational changes, resulting in increases (benzodiazepine agonists) or decreases (benzodiazepine inverse agonists) in the effects of the inhibitory transmitter γ-aminobutyric acid (GABA). This concept has been widely accepted. We have now studied the effects of inverse agonists after chronic treatment with inverse agonists themselves and with benzodiazepine agonists, in order to see if tolerance develops (as seen with the agonists) or whether an opposite change occurs.
authors.affiliation: Department of Pharmacology, The Medical School, University Walk, Bristol.
authors.forename: H J
authors.initials: HJ
authors.lastname: Little
authors.forename: D J
authors.initials: DJ
authors.lastname: Nutt
authors.forename: S C
authors.initials: SC
authors.lastname: Taylor