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A three-state model of the benzodiazepine receptor explains the interactions between the benzodiazepine antagonist Ro 15-1788, benzodiazepine tranquilizers, β-carbolines, and phenobarbitone

The potent benzodiazepine receptor ligands β-carboline-3-carboxylic acid ethyl ester (β-CCM) and the corresponding methylester (β-CCM) administered i.v. depressed segmental dorsal root potentials in spinal cats, reversed the prolongation of dorsal root potentials by phenobarbitone, and abolished the depression of a motor performance task induced by phenobarbitone in mice; β-CCE enhanced the low-frequency facilitation of pyramidal population spikes in the hippocampus of anaesthetized rats. These effects of β-carbolines reflect a depression of GABAergic synaptic transmission and, thus, are diametrically opposed to the enhancing action of benzodiazepine tranquilizers. The specific benzodiazepine antagonist, Ro 15-1788, while not affecting dorsal root potentials, hippocampal population spikes or phenobarbitone-induced motor performance depression, abolished the effects of β-CCE on the three parameters and similar effects of β-CCM on the spinal cord and motor performance.

A three-state model of the benzodiazepine receptor is proposed in which benzodiazepine tranquilizers act as agonists enhancing the function of the benzodiazepine receptor as a coupling unit between GABA receptor and chloride channel, β-carbolines act as “inverse agonists” reducing this coupling function, and Ro 15-1788 represents a competitive antagonist blocking both the enhancing effect of agonists and the depressant effect of “inverse agonists” on GABAergic synaptic transmission.

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• Ahlquist J, Brown MW, Rose D (1982) The effects of amnesia-producing drugs on hippocampal potentiation in the rat. Br J Pharmacol 75:48P

  Google Scholar 

• Ben-Ari Y, Krnjevic K, Reinhardt W (1979) Hippocampal seizures and failure of inhibition. Can J Physiol Pharmacol 57:1462–1466

  Google Scholar 

• Bernhard P, Bergen K, Sobiski R, Robson RD (1981) CGS 8216 (2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one), an orally effective benzodiazepine antagonist. Pharmacologist 23:150

  Google Scholar 

• Besson J-M, Rivot J-P, Aleonard P (1971) Action of picrotoxin on presynaptic inhibition of various origins in the cat's spinal cord. Brain Res 26:212–216

  Google Scholar 

• Bonetti EP, Pieri L, Cumin R, Schaffner R, Pieri M, Gamzu ER, Müller RKM, Haefely W (1982) Benzodiazepine antagonist Ro 15-1788: Neurological and behavioral effects. Psychopharmacology 78: 8–18

  Google Scholar 

• 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

  Google Scholar 

• Braestrup C, Schmiechen R, Neef G, Nielsen M, Petersen EN (1982) Interaction of convulsive ligands with benzodiazepine receptors. Science 216:1241–1243

  Google Scholar 

• Cepeda C, Tanaka T, Besselièvre R, Potier P, Naquet R, Rossier J (1981) Proconvulsant effects in baboons of β-carboline, a putative endogenous ligand for benzodiazepine receptors. Neurosci Lett 24:53–57

  Google Scholar 

• Choi DW, Farb DH, Fischbach GD (1981) Chlordiazepoxide selectively potentiates GABA conductance of spinal cord and sensory neurons in cell culture. J Neurophysiol 45:621–631

  Google Scholar 

• Costa E, Guidotti A (1979) Molecular mechanisms in the receptor action of benzodiazepines. Ann Rev Pharmacol Toxicol 19:531–545

  Google Scholar 

• Courvoisier S (1956) Pharmacodynamic basis for the use of chlorpromazine in psychiatry. J Clin Exp Psychopathol 17:25–37

  Google Scholar 

• Cowen PJ, Green AR, Nutt DJ, Martin IL (1981) Ethyl-β-carboline carboxylate lowers seizure threshold and antagonizes flurazepaminduced sedation in rats. Nature 290:54–55

  Google Scholar 

• Gee KW, Yamamura H (1982) A novel pyrazoloquinoline that interacts with brain benzodiazepine receptors: characterization of some in vitro and in vivo properties of CGS 9896. Life Sci 30:2245–2252

  Google Scholar 

• Haefely W, Polc P, Schaffner R, Keller HH, Pieri L, Möhler H (1979) Facilitation of GABAergic transmission by drugs. In: Krogsgaard-Larsen P, Scheel-Krüger J, Kofod H (eds) GABA-Neurotransmitters. Munksgaard, Copenhagen, pp 357–375

  Google Scholar 

• Haefely W, Pieri L, Polc P, Schaffner R (1981a) General pharmacology and neuropharmacology of benzodiazepine derivatives. In: Hoffmeister F, Stille G (eds) Handbook of experimental pharmacology; Psychotropic agents, vol 55, Part 2. Springer, Berlin Heidelberg New York, pp 13–262

  Google Scholar 

• Haefely W, Schaffner R, Pole P, Pieri L (1981b) General pharmacology and neuropharmacology of propanediol carbamates. In: Hoffmeister F, Stille G (eds) Handbook of experimental pharmacology; Psychotropic agents, vol 55, Part 2. Springer, Berlin Heidelberg New York, pp 265–283

  Google Scholar 

• Hunkeler W, Möhler H, Pieri L, Polc P, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290:514–516

  Google Scholar 

• Jones BJ, Oakley NR (1981) The convulsant properties of methyl-β-carboline-3-carboxylate in the mouse. Br J Pharmacol 74:884P-885P

  Google Scholar 

• Macdonald RL, Barker JL (1979) Enhancement of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: a common mode of anticonvulsant action. Brain Res 167:323–336

  Google Scholar 

• McMillan JA, Mokha SS (1982) Effects of bicuculline on dorsal root potentials in the cat. J Physiol (London) 322:34P

  Google Scholar 

• Möhler H, Richards JG (1981) Agonist and antagonist benzodiazepine receptor interaction in vitro. Nature 294:763–765

  Google Scholar 

• 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

  Google Scholar 

• Nicoll RA (1978) Selective actions of barbiturates on synaptic transmission. In: Lipton MA, DiMascio A, Killam KF (eds) Psychopharmacology: A generation of progress. Raven Press, New York, pp 1337–1348

  Google Scholar 

• Nicoll RA, Alger BE (1979) Presynaptic inhibition: transmitter and ionic mechanisms. Int Rev Neurobiol 21:217–258

  Google Scholar 

• Nutt DJ, Cowen PJ, Little HJ (1982) Unusual interactions of benzodiazepine receptor antagonists. Nature 295:436–438

  Google Scholar 

• Oakley NR, Jones BJ (1980) The proconvulsant and diazepam-reversing effects of ethyl-β-carboline-3-carboxylate. Eur J Pharmacol 68:381–382

  Google Scholar 

• O'Brien RA, Schlosser W, Spirt NM, Franco S, Horst WD, Polc P, Bonetti EP (1981) Antagonism of benzodiazepine receptors by beta carbolines. Life Sci 29:75–82

  Google Scholar 

• Olsen RW (1981) GABA-benzodiazepine-barbiturate receptor interactions. J Neurochem 37:1–13

  Google Scholar 

• Polc P, Laurent J-P, Scherschlicht R, Haefely W (1981a) Electrophysiological studies on the specific benzodiazepine antagonist Ro 15-1788. Naunyn-Schmiedeberg's Arch Pharmacol 316:317–325

  Google Scholar 

• Polc P, Ropert N, Wright DM (1981b) Ethyl β-carboline-3-carboxylate antagonizes the action of GABA and benzodiazepines in the hippocampus. Brain Res 217:216–220

  Google Scholar 

• Skerritt JH, Willow M, Johnston GAR (1982) Diazepam enhancement of low affinity GABA binding to rat brain membranes. Neurosci Lett 29:63–66

  Google Scholar 

• Study RE, Barker JL (1981) Diazepam and (−)-pentobarbital: Fluctuation analysis reveals different mechanisms for potentiation of γ-amino-butyric acid responses in cultured central neurons. Proc Natl Acad Sci USA 78:7180–7184

  Google Scholar 

• Supavilai P, Mannonen A, Karobath M (1982) Modulation of GABA binding sites by CNS depressants and CNS convulsants. Neurochem Int 4:259–268

  Google Scholar 

• Tenen SS, Hirsch JD (1980) β-Carboline-3-carboxylic acid ethyl ester antagonizes diazepam activity. Nature 28:609–610

  Google Scholar 

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1. Pharmaceutical Research Department, F. Hoffmann-La Roche & Co. Ltd., Grenzacher Strasse 124, CH-4002, Basel, Switzerland

   Petar Polc, Erico Pietro Bonetti, Rudolf Schaffner & Willy Haefely

1. Petar Polc
2. Erico Pietro Bonetti
3. Rudolf Schaffner
4. Willy Haefely

Polc, P., Bonetti, E.P., Schaffner, R. et al. A three-state model of the benzodiazepine receptor explains the interactions between the benzodiazepine antagonist Ro 15-1788, benzodiazepine tranquilizers, β-carbolines, and phenobarbitone. Naunyn-Schmiedeberg's Arch. Pharmacol. 321, 260–264 (1982). https://doi.org/10.1007/BF00498510

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• Received: 10 August 1982

• Accepted: 03 November 1982

• Issue Date: December 1982

• DOI: https://doi.org/10.1007/BF00498510

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