Abstract
Both the anticonvulsant and sedative effects of diazepam (5 mg/kg) were reversed by subsequent administration of the suggested specific benzodiazepine antagonist Ro 15-1788. In contrast neither the seizure threshold raising or sedative effect of melatonin (200 mg/kg) was reversed by Ro 15-1788. Ro 15-1788 had no effect on the convulsant action of the benzodiazepine Ro 05-3663. These data therefore argue against the suggestion that melatonin produces its sedative and anticonvulsant effects in vivo by interacting with the benzodiazepine receptor, and also strengthens the suggestion that Ro 05-3663 does not act at this site. The use of Ro 15-1788 in demonstrating whether a drug acts in vivo at the benzodiazepine site to produce a pharmacological response is discussed.
References
Braestrup C, Nielsen M, Olsen CE (1980) Urinary and brain β-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors. Proc Natl Acad Sci USA 77:2288–2292
Cowen PJ, Green AR, Nutt DJ, Martin IL (1981) Ethyl β-carboline carboxylate lowers seizure threshold and antagonises flurazepam-induced sedation in rats. Nature 290:54–55
Hunkeler W, Möhler H, Pieri L, Polc P, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290:515–516
Marangos PJ, Patel J, Hirata F, Sondheim D, Paul SM, Skolnick P, Goodwin FK (1981) Inhibition of diazepam binding by tryptophan derivatives including melatonin and its brain metabolite N-acetyl-5-methoxy kynurenamine. Life Sci 29:259–267
Möhler H, Burkard WP, Keller HH, Richards JG, Haefely W (1981) Benzodiazepine antagonist Ro 15-1788: Binding characteristics and interaction with drug induced changes in dopamine turnover and cerebellar cGMP levels. J Neurochem 37:714–722
Möhler H, Richards JG (1981) Agonist and antagonist benzodiazepine receptor interactions in vitro. Nature 294:763–765
Nielsen M, Braestrup C (1980) Ethyl β-carboline-3-carboxylate shows differential benzodiazepine receptor interaction. Nature 286:606–607
Nutt DJ, Cowen PJ, Green AR (1980) On the measurement in rats of the convulsant effect of drugs and the changes which follow electroconvulsive shock. Neuropharmacology 19:1017–1023
Nutt DJ, Cowen PJ, Green AR (1981) Studies on the post-ictal rise in seizure threshold. Eur J Pharmacol 71:287–295
Nutt DJ, Cowen PJ, Little HJ (1982) Unusual interactions of benzodiazepine receptor antagonists. Nature 295:436–438
O'Brien RA, Spirt NM (1980) The inhibition of GABA-stimulated benzodiazepine binding by a convulsant benzodiazepine. Life Sci 26:1441–1445
Olsen R, Leeb-Lundberg F (1981) Convulsant and anticonvulsant drug binding sites related to the GABA receptor/ionophore system. In: Morselli, PL, Löscher W, Meldrum B, Reynolds EH (eds) Neurotransmitters, seizures and epilepsy. Raven Press, New York, pp 165–173
Simmonds MA (1980) A site for the potentiation of GABA-mediated responses by benzodiazepines. Nature 283:558–560
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Green, A.R., Nutt, D.J. & Cowen, P.J. Using Ro 15-1788 to investigate the benzodiazepine receptor in vivo: Studies on the anticonvulsant and sedative effect of melatonin and the convulsant effect of the benzodiazepine Ro 05-3663. Psychopharmacology 78, 293–295 (1982). https://doi.org/10.1007/BF00428169
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00428169