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Pharmacology of Sedatives, Hypnotics, and Anxiolytics

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Handbook of Substance Abuse

Abstract

This chapter is concerned with the pharmacology of agents that are used therapeutically for the treatment of a variety of disorders including anxiety, sleep, and psychosomatic disorders, and for sedation, skeletal muscle relaxation, and for the treatment of epilepsy. The distinct classification of these agents as sedatives, hypnotics, and anxiolytics is clouded since they have overlapping pharmacologie activities. For example, some agents, particularly certain benzodiazepines, can be used therapeutically either to treat the aforementioned conditions or achieve the effects mentioned to one degree or another. The drugs that are discussed include the benzodiazepines (full and partial agonists, full and partial inverse agonists, and antagonists), buspirone, zolpidem, selected barbiturates, and other sedative-hypnotics of diverse chemical structures.

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References

  • Abbruzzese, A., & Swanson, J. (1965). Jaundice after therapy with chlordiazepoxide hydrochloride.New England Journal of Medicine.273, 321–322.

    Article  CAS  PubMed  Google Scholar 

  • Amin, J., & Weiss, D. S. (1993). GABA, receptor needs two homologous domains of the (3-subunit for activation by GABA but not by pentobarbital.Nature,366, 565–569.

    Article  CAS  PubMed  Google Scholar 

  • Andersson, L. C., Lehto, V. P., Stenman, S., Badley, R. A., & Virtanen, I. (1981). Diazepam induces mitotic arrest at prometaphase by inhibiting centriolar separation.Nature,291, 247–248.

    Article  CAS  PubMed  Google Scholar 

  • Andrada-Martinez, R., Marquez-Orozco, M. C., & Marquez-Orozco, A. (1993). Cerebellar histological changes produced by diazepam.Proceedings of the Western Pharmacology Society,36, 219–225.

    CAS  PubMed  Google Scholar 

  • Arbilla, S., Depoortere, H., George, P., & Langer, S. Z. (1985). Pharmacological profile of the imidazopyridine zolpidem at benzodiazepine receptors and electrocorticogram in rats.Archives of Pharmacology,330, 248–251.

    Article  CAS  PubMed  Google Scholar 

  • Ashton, H. (1984). Benzodiazepine withdrawal: An unfinished story.British Medical Journal.288, 1135–1140.

    Article  CAS  PubMed  Google Scholar 

  • Bakti, G., Fisch, H. U., Karlaganis, G., Minder, C., & Bircher, J. (1987). Mechanism of the excessive sedative response of cirrhotics to benzodiazepines: Model experiments with triazolam.Hepatology,7, 629–638.

    Article  CAS  PubMed  Google Scholar 

  • Barnas, C., Whitworth, A. B., & Fleischhacker, W. W. (1993). Are patterns of benzodiazepines use predictable?Psychopharmacology,111, 301–305.

    Article  CAS  PubMed  Google Scholar 

  • Basile, A. S., Jones, E. A., & Skolnick, P. (1991). The pathogenesis and treatment of hepatic encephalopathy: Evidence for the involovement of benzodiazepine receptor ligands.Pharmacological Reviews,43, 27–71.

    CAS  PubMed  Google Scholar 

  • Bell, J. A., & Anderson E. G. (1972). The influence of semicarbazide-induced depletion of y-aminobutyric acid on presynaptic inhibition.Brain Research 43, 161 - 169.

    Article  CAS  PubMed  Google Scholar 

  • Bianchi, G., & Steiner, P. (1992). A clinical double-blind study of flumazenil, antagonist of benzodiazepines in loco-regional anesthesia.Acta Anesthesthesiologica Belgica,43, 121–129.

    CAS  Google Scholar 

  • Bitran, D., Primus, R. J., & Kellogg, C. K. (1991). Gestational exposure to diazepam increases sensitivity to convulsants that act at the GABA/benzodiazepine receptor complex.European Journal of Pharmacology,196, 223–231.

    Article  CAS  PubMed  Google Scholar 

  • Boisse, N. R., & Okamoto, M. (1978a). Physical dependence to barbital compared to pentobarbital “Chronically equivalent” dosing method.Journal of Pharmacology and Experimental Therapeutics,204, 497–506.

    CAS  Google Scholar 

  • Boisse, N. R., & Okamoto, M. (1978b). Physical dependence to barbital compared to pentobarbital: IV. Influence of elimination kinetics.Journal of Pharmacology and Experimental Therapeutics,204, 526–540.

    CAS  Google Scholar 

  • Bourguignon, J. (1993). Endogenous and synthetic ligands of mitochondria) benzodiazepine receptors: Structure-affinity relationships. In E. Geisen-Crouse (Ed.),Peripheral benzodiazepine receptors(pp. 59–82 ). New York: Academic Press.

    Google Scholar 

  • Braestrup, C. (1981). Biochemical effects of anxiolytics. In F. Hoffmeister, G. Stille (Eds.),Handbook of experimental pharmacology(Vol. 55/II, pp. 293–319 ). Berlin: Springer-Verlag.

    Google Scholar 

  • Branch, R. A., Morgan, M. H., Jones, J., & Read, A. E. (1976). Intravenous administration of diazepam in patients with chronic liver disease.Gut,17, 975–983.

    Article  CAS  PubMed  Google Scholar 

  • Briemer, L. T. M., Burm, A. G. L., Danhof, M., Hennis, P. J., Vletter, A. A., de Voogt, J. H., Spierdijk, J., & Bovill, J. G. (1991). Pharmacokinetic-pharmacodynamic modelling of the interaction between flumazenil and midazolam in volunteers by aperiodic EEGanalysis. Clinical Pharmacokinetics,22(6), 497–508.

    Article  Google Scholar 

  • Bucher, J. R., Shackelford, C. C., Haseman, J. K., Johnson, J. D., Kurtz, P. J., & Persing, R. L. (1994). Carcinogenicity studies of oxazepam in mice.Fundamental and Applied Toxicology,23, 280–297.

    Article  CAS  PubMed  Google Scholar 

  • Buchsbaum, M. S., Hazlett, E., Sicotte, N., Stein, M., Wu, J., & Zetin, M. (1985). Topographic EEG changes with benzodiazepine administration in generalized anxiety disorder.Biological Psychiatry,20, 832–842.

    Article  CAS  PubMed  Google Scholar 

  • Byrnes, J. J., & Miller, L. G. (1993). Prenatal benzodiazepine exposure: Ill. Lorazepam exposure is associated with a shift toward inverse agonist efficacy.Journal of Psychopharmacology,7, 39–42.

    CAS  PubMed  Google Scholar 

  • Cacioppo, J., & Merlis, S. (1961). Chlordiazepoxide hydrochloride (librium) and jaundice: Report of a case.American Journal of Psychiatry,117, 1040–1041.

    CAS  PubMed  Google Scholar 

  • Cadranel, J. E, Younsi, M. E., Pidoux, B., Zylberberg, P., Benhamou, Y., Valla, D., & Opolon, P. (1995). Flumazenil therapy for hepatic encephalopathy in cirrhotic patients: A double-blind pragmatic randomized, placebo study.European Journal of Gastroenterology and Hepatology,7, 325–329.

    CAS  PubMed  Google Scholar 

  • Calvo, D. J., & Medina, J. H. (1992). Regulation of peripheral-type benzodiazepine receptors following repeated benzodiazepine administration.Functional Neurology, 7, 227–230.

    CAS  PubMed  Google Scholar 

  • Chesley, S., Lumpkin, M., Schatzki, A., Galpern, W. R., Greenblatt, D. J., Shader, R. I., & Miller, L. G. (1991). Prenatal exposure to benzodiazepine: I. Prenatal exposure to lorazepam in mice alters open-field activity and GABAA receptor function.Neuropharmacology,30, 53–58.

    Article  CAS  PubMed  Google Scholar 

  • Chiu, T. H., Tietz, E. 1., & Rosenberg, H. C. (1987). Benzodiazepines. In I. K. Ho (Ed.),Toxicology of CNS depressants(pp. I-32). Boca Raton, FL: CRC.

    Google Scholar 

  • Chiu, T. H., & Rosenberg, H. C. (1995). Barbiturates and benzodiazepines: Effects and mechanisms. In L. W. Chang & R. S. Dyer (Eds),Handbook of neurotoxicology(pp. 739–767 ). New York: Dekker.

    Google Scholar 

  • Cittadini, A., & Lader, M. (1991). Lack of effect of a small dose of flumazenil in reversing short-term tolerance to benzodiazepines in normal subjects.Journal of Psychopharmacology, 5, 220–227.

    Article  CAS  PubMed  Google Scholar 

  • Cobden, 1., Record, C. O., & White, R. W. B. (1981). Fatal interhepatic choleostasis associated with triazolam.Postgraduate Medical Journal,57, 730–731.

    Article  CAS  PubMed  Google Scholar 

  • Cunningham, M. L. (1965). Acute hepatic necrosis following treatment with amitriptyline and diazepam.American Journal of Psychiatry,111, 1107–1109.

    Article  CAS  Google Scholar 

  • Curtis, D. R., Duggan, A. W, Felix D., & Johnston, G. A. R. (1971). Bicuculline, an antagonist of GAGA and synaptic inhibition in the spinal cord.Brain Research,32, 69–96.

    Article  CAS  PubMed  Google Scholar 

  • De la Iglesia, A., Barsoum, N., Gough, A., Mitchell, L., Martin, R. A., di Fonzo, C., & McGuire, E. J. (1981). Carcinogenesis bioassay of prazepam (Verstran) in rats and mice.Toxicology Applied Pharmacology,57, 39–54.

    Article  Google Scholar 

  • Dennis, T., Dubois, A., Benavides, J., & Scatton, B. (1988). Distribution of central co, (Benzodiazepine,) and wZ (Benzodiazepine2) receptor subtypes in the monkey and human brain. An autoradiographic study with [’H]Flunitrazepam and the w, selective ligand [3H]Zolpidem.Journal of Pharmacology and Experimental Therapy,247, 309–322.

    CAS  Google Scholar 

  • Derlet, R. W, & Albertson, T. E. (1994). Flumazenil induces seizures and death in mixed cocaine-diazepam intoxications.Annals of Emergency Medicine,23, 494–498.

    Article  CAS  PubMed  Google Scholar 

  • de Wit, H., & Griffiths, R. R. (1991). Testing the abuse liability of anxiolytic and hypnotic drugs in humans.Drug and Alcohol Dependence,28, 83–111.

    Article  PubMed  Google Scholar 

  • Diana, G., & Massotti, M. (1992). Repeated administration of diazepam reduces [3H]Ro 5–4864 binding in cerebral cortex of rats.Pharmacology,Biochemistry and Behavior,42, 297–300.

    Article  CAS  Google Scholar 

  • Dimpfel, W., Spüler, M., Nickel, B. (1986). Radioelectroencephalography (tele-stereo-EEG) in the rat as a pharmacological model to differentiate the central action of flupirtine from that of opiates, diazepam and phenobarbital.Neuropsychobiology,16, 163–168.

    Article  CAS  PubMed  Google Scholar 

  • Doble, A., & Martin, I. L. (1992). Multiple benzodiazepine receptors: No reason for anxiety.TiPS,13, 76–78.

    CAS  PubMed  Google Scholar 

  • Doble, A., Malgouris, C., Daniel, M., Daniel, N., Imbault, E, Basbaum, A., Uzan, A., Guérémy, C., & Le Fur, G. (1987). Labelling of peripheral-type benzodiazepine binding sites in human brain with [3H]PK 11195: Anatomical and subcellular distribution.Brain Research Bulletin,18, 49–61.

    Article  CAS  PubMed  Google Scholar 

  • Domino, E. F., French, J., Pohorecki, R., Galus, C. E, & Pandit, S. K. (1989). Further observations on the effects of subhypnotic doses of midazolam in normal volunteers.Psychopharmacology,25, 460–465.

    CAS  Google Scholar 

  • Essig, C. F. (1967). Clinical and experimental aspects of barbiturate withdrawal convulsions.Epilepsia,8, 21–30.

    Article  CAS  PubMed  Google Scholar 

  • Evans, S. M., Funderburk, F. R., & Griffiths, R. R. (1990). Zolpidem and triazolam in humans: Behavioral and subjective effects and abuse liability.Journal of Pharmacology and Experimental Therapeutics,255, 1246–1255.

    CAS  PubMed  Google Scholar 

  • Fialip, J., Aumaitre, O., Eschalier, A., Maradeix, B., Dordain, G., & Lavarenne, J. (1987). Benzodiazepine withdrawal seizures: Analysis of 48 case reports.Clinical Neuropharmacologv,6, 536–544.

    Google Scholar 

  • File, S. E. (1990). The history of benzodiazepine dependence: A review of animal studies.Neuroscience and Biohehavioral Review,14, 135–146.

    Article  CAS  Google Scholar 

  • File, S. E., & Baldwin, H. A. (1989). Changes in anxiety in rats tolerant to, and withdrawn from, benzodiazepines: Behavioural and biochemical studies. In R Tyrer, (Ed.),Psychopharmacology of anxiety(pp. 28–51 ). Oxford, England: Oxford University Press.

    Google Scholar 

  • File, S. E., & Pellow, S. (1986). Intrinsic actions of the benzodiazepine receptor antagonist Ro 15–1788.Psychopharmacology,88, 1–11.

    Article  CAS  PubMed  Google Scholar 

  • Fink, M., Irwin, P., Weinfeld, R. E., Schwartz, M. A., & Conney, A. H., (1976). Blood levels and electroencephalographic effects of diazepam and bromazepam.Clinical Pharmacology Therapeutics,20, 184–191.

    CAS  Google Scholar 

  • Fox, K. A., & Lahcen, R. B. (1974). Liver-cell adenomas and peliosis hepatis in mice associated with oxazepam.Research Communications in Chemical Pathology and Pharmacology,8, 481–488.

    CAS  PubMed  Google Scholar 

  • Friedman, H., Greenblatt, D. J., Peters, G. R., Metzler, C. M., Charlton, M. D., Harmatz, J. S., Antal, E. J., Sanborn, E. C., & Francom, S. F. (1992). Pharmacokinetics and pharmacodynamics of oral diazepam: Effects of dose, plasma concentration, and time.Clinical Pharmacology Therapeutics,52, 139–150.

    Article  CAS  Google Scholar 

  • Gallager, D. W., & Primus, R. J. (1993). Benzodiazepine tolerance and dependence: GABAA receptor complex locus of change. In S. Wonnacott & G. Glunt (Eds.),Neurochemistry of drug dependence(pp. 135–151 ). London: Portland.

    Google Scholar 

  • Gallager, D. W., Heninger, K., & Heninger, G. (1986). Periodic benzodiazepine antagonist administration prevents benzodiazepine withdrawal symptoms in primates.European Journal of Pharmacology 132, 31 - 38.

    Article  CAS  PubMed  Google Scholar 

  • Gallager, D. W., Jacobs, A. A., Crais, J. S., During, M. J., & Hernandez, T. D. (1991). Chronic treatments that produce reversible and irreversible changes in gamma-aminobutyric acid sensitivity. In E. A. Bernard & E. Costa (Eds.),Transmitter amino acid receptors,structures,transactions and model(pp. 113–128 ). New York: Raven.

    Google Scholar 

  • Gallager, D. W, Marley, R. J., & Hernandez, T. D. (1991). Biochemical and electrophysiological mechanisms underlying benzodiazepine tolerance and dependence. In J. Pratt (Ed.),The biological bases of drug tolerance and dependence(pp. 49–70 ). London: Academic Press.

    Google Scholar 

  • Gardner, C. R., Tully, W. R., & Hedgecock, C. J. R. (1993). The rapidly expanding range of neuronal benzodiazepine receptor ligands.Progress in Neurobiology 40, 1 - 61.

    Article  CAS  PubMed  Google Scholar 

  • Gavish, M., Bar-Ami, S., & Weitzman, R. (1992). The endocrine system and mitochondrial benzodiazepine receptors.Molecular and Cellular Endocrinology 88, 1 - 13.

    Article  CAS  PubMed  Google Scholar 

  • Gavish, M., Bar-Ami, S., & Weitzman, R. (1993). Pathophysiological and endocrinological aspects of peripheral-type benzodiazepine receptors. In E. Giesen-Crouse (Ed.),Peripheral benzodiazepine receptors(pp. 210227 ). London: Academic Press.

    Google Scholar 

  • Glaser, G. H., Penry, J. K., & Woodbury, D. M. (1980).Antiepileptic drugs: Mechanisms of action. New York: Raven.

    Google Scholar 

  • Gonsalves, S. F., & Gallager, D. W. (1988). Persistent reversal of tolerance to anticonvulsant effects and GABAergic subsensitivity by a single exposure to benzodiazepine antagonist during chronic benzodiazepine administration.Journal of Pharmacology and Experimental Therapy,244, 79–83.

    CAS  Google Scholar 

  • Grant, S. J., Galloway, M. P., Mayor, R., Fenerty. J. R, Finkelstein, M. F., Roth, R. H., & Redmond, D. E. Jr. (1985). Precipitated diazepam withdrawal elevates noradrenergic metabolism in primate brain.European Journal of Pharmacology,107, 127–132.

    Article  CAS  PubMed  Google Scholar 

  • Greenblatt, D. J., Shader, R. I. (1985). Clinical pharmacokinetics of the benzodiazepines. In D. E. Smith & D. R. Wesson (Eds.),The benzodiazepines: Current standards for medical practice(pp. 43–64 ). Lancaster, England: MTP.

    Chapter  Google Scholar 

  • Griffiths, R. R. (1995). Commentary on review by Woods and Winger. Benzodiazepines: Long-term use among patients is a concern and abuse among polydrug abusers is not trivial [Letter to the editor].Psvchopharmacology,118, 116–117.

    Article  CAS  Google Scholar 

  • Griffiths, R. R., & Wolf, B. (1990). Relative abuse liability of different benzodiazepines in drug abusers.Journal of Clinical Psychopharmacology,10(4), 237–243.

    CAS  PubMed  Google Scholar 

  • Haefely, W. E. (1977). Synaptic pharmacology of barbiturates and benzodiazepines.Agents Actions,7, 353–359.

    Article  CAS  PubMed  Google Scholar 

  • Haefely, W. (1986). Biological basis of drug induces tolerance, rebound, and dependence. Contribution of recent research on benzodiazepines.Pharmacopsychiatria(Stuttgart),19, 353–361.

    CAS  Google Scholar 

  • Haefely, W. E. (1990). The GABAA-benzodiazepine receptor: Biology and pharmacology. In G. D. Brown, M. Ruth, & R. Noyer (Eds.),Handbook of anxiety: Vol. 3 The neurobiology of anxiety(pp. 165–188 ). Amsterdam: Elsevier.

    Google Scholar 

  • Haefely, W, Kyburz, E., Gerecke, M., & Möhler, H. (1985). Recent advances in the molecular pharmacology of benzodiazepine receptors and in the structure-activity relationships of their agonists and antagonists. In B.Testa (Ed.),Advances in drug research(Vol. 14, pp. I65–322 ). London: Academic Press.

    Google Scholar 

  • Haefely, W. Martin, J. R., & Schoch, P. (1990). Novel anxiolytics that act as partial agonists at benzodiazepine receptors.TiPS,11, 452–456.

    PubMed  Google Scholar 

  • Hallstrom, C., & Lader, M. (1981). Benzodiazepine withdrawal phenomena.International Pharmacopsychiatry,16, 235–244.

    CAS  PubMed  Google Scholar 

  • Herings, R. M. C., Stricker, B. H.. de Boer, A., Bakker, A., & Sturmans, E. (1995). Benzodiazepines and the risk of falling leading to femur fractures.Archives of Internal Medicine,155, 1801–1807.

    Article  CAS  Google Scholar 

  • Hernandez-Alvarez, L. A. I., Marquez-Orozco, M. C., Marquez-Orozco, A., & Hicks, J. J. (1991). Efectos teratolbgicos de las benzodiazepinas.Ginecologia y Obstetricia de Mexico,59, 195–201.

    CAS  PubMed  Google Scholar 

  • Hernandez-Alvarez, L. A. I., Marquez-Orozco, M. C., & Marquez-Orozco, A. (1994). Mating behavior of female mice treated prenatally with diazepam.Proceedings of the Western Pharmacology Society,37, 69–71.

    CAS  PubMed  Google Scholar 

  • Herrmann, W. M., & Schaerer, E. (1986). Pharmaco-EEG: Computer EEG analysis to describe the projection of drug effects on a functional cerebral level in humans. In F. H. Lopes da Silva, W. Storm van Leevwen, & A. Redmond (Eds.),Handbook ofelectroencephalography and clinical neurophvsiolog: Vol. 2. Clinical applications of computer analysis of EEG and other neurophysiological signals(pp. 385–445 ). Amsterdam: Elsevier.

    Google Scholar 

  • Hertz, L. (1993). Binding characteristics of the receptor and coupling to transport proteins. In E. GiesenCrouse (Ed.),Peripheral benzodiazepine receptors(pp. 27–57 ). London: Academic Press.

    Google Scholar 

  • Hines, L. R. (1981). Toxicology and side-effects of anxiolytics. In F. Hoffmeister & G. Stille (Eds.),Handbook of experimental pharmacology(Vol. 55/II, pp. 359–393 ). Berlin: Springer-Verlag.

    Google Scholar 

  • Ho, I. K. (1987). Barbiturate sedative-hypnotics. In I. K. Ho (Ed.),Toxicology of CNS depressants(pp. 33–55 ). Boca Raton, FL: CRC.

    Google Scholar 

  • Ho, I. K., & Harris, R. A. (1981). Mechanism of action of barbiturates.Annual Review of Pharmacology and Toxicology,21, 83–111.

    Article  CAS  PubMed  Google Scholar 

  • Hobbs, W. R., Rall, T. W, & Verdoorn, T. A. (1996). Hypnotic, and sedatives; Ethanol. In J. G. Hardman, L. E. Limbird, P. B. Molinoff, R. W. Ruddon, & A. Goodman Gillman (Eds.),Goodman Gilntans the pharmacological basis of therapeutics(pp. 361–430 ). New York: McGraw-Hill.

    Google Scholar 

  • Hollister, L. E. (1985). Principles of therapeutic applications of benzodiazepines. In D. E. Smith & D. R. Wesson (Eds.),The benzodiazepines current standards for medical practice(pp. 87–96 ). Lancaster, England: MTP.

    Chapter  Google Scholar 

  • Hollister, L. E., & Csernansky, J. G. (1990).Clinical pharmacology of psychotherapeutic drugs( 3rd ed. ). New York: Churchill Livingstone.

    Google Scholar 

  • Hollister, L. E., Muller-Oerlinghausen, B., Rickels, K., & Shader, R. I. (1993). Clinical uses of benzodiazepines.Journal of Clinical Psvchopharmacology,13, 1–169.

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Iguchi, M. Y., Handelsman, L., Bickel, W. K., & Griffiths, R. R. (1993). Benzodiazepine and sedative use/abuse by methadone maintenance clients.Drug and Alcohol Dependence,32, 257–266.

    Article  CAS  PubMed  Google Scholar 

  • Isbell, H.. & Fraser, H. F., (1950). Addiction to analgesics and barbiturates.Journal of Pharmacology and Experimental Therapeutics,99, 355–397.

    CAS  PubMed  Google Scholar 

  • Iwaya, N., Morita, Y., & Miyoshi, K. (1989). Determination of pharmoco-dynamics of diazepam by quantitative pharmaco-EEG.Japanese Journal of Psychiatry and Neurology,43, 675–684.

    CAS  PubMed  Google Scholar 

  • Jaffe, J. H., Ciraulo, D. A., Nies, A., Dixon, R. B., & Monroe, L. L. (1983). Abuse potential of halazepam and of diazepam in patients recently treated for acute alcohol withdrawal.Clinical Pharmacology Therapeutics,34, 623–630.

    Article  CAS  Google Scholar 

  • Judd, F. K., Norman, T. R., Marriott, P. F., & Burrows, G. D. (1986). A case of alprazolam-related hepatitis.American Journal of Psychiatry,143. 388–389.

    CAS  PubMed  Google Scholar 

  • Judd, F. K., Norman, T. R., & Burrows, G. D. (1990). Pharmacotherapy of panic disorder.International Review of Psychiatry,2, 399–409.

    Article  Google Scholar 

  • Juergens, S. M. (1993). Benzodiazepines and addiction.Psychiatric Clinics of North America,16, 75–86.

    CAS  PubMed  Google Scholar 

  • Kay, D. C., Blackburn, A. B., Buckingham, J. A., & Kara-can, I. (1976). Human pharmacology of sleep. In R. L. Williams & I. Karacan (Eds.),Pharmacology of sleep(pp. 83–210 ). New York: Wiley.

    Google Scholar 

  • Kellogg, C. K., Taylor, M. K., Rodriguez-Zafra, M., & Pleger, G. L. (1993). Altered stressor-induced changes in GABAA receptor function in the cerebral cortex of adult rats exposed in utero to diazepam.Pharmacology,Biochemistry and Behavior,44, 267–273.

    Article  CAS  Google Scholar 

  • King, M. B., Gabe, J., Williams, P., & Rodrigo, E. K. (1990). Long term use of benzodiazepines: The views of patients.British Journal of General Practice,40, 194–196.

    CAS  PubMed  Google Scholar 

  • Kinoshita, T., Michel, C. M., Yagyu, T., Lehmann, D., & Saito, M. (1994). Diazepam and sulpiride effects on frequency domain EEG source locations.Neuropsychobiology,30, 126–131.

    Article  CAS  PubMed  Google Scholar 

  • Klepner, C. A., Lippa, A. S., Benson, D. I., Sano, M. C., & Beer, B. (1979). Resolution of two biochemically and pharmacologically distinct benzodiazepine receptors.Pharmacology,Biochemistry and behavior; 11, 457 – 462.

    Article  CAS  Google Scholar 

  • Koff J. M., & Miller, L. G. (1995). Prenatal lorazepam exposure: 4. Persistent alterations in pentylenetetrazoleinduced seizure threshhold and GABA-dependent chloride uptake after prenatal lorazepam exposure.Pharmacology,Biochemistry and Behavior,51, 721–724.

    Article  CAS  Google Scholar 

  • Krueger, K. E., & Papadopoulos, V. (1993). The role of mitochondria) benzodiazepine receptors in steriodogenesis. In E. Giesen-Crouse (Ed.),Peripheral benzodiazepine receptors(pp. 89–109 ). London: Academic Press.

    Google Scholar 

  • Lader, M. (1995). Commentary on review by Woods and Winger entitled “Current benzodiazepine issues” [Letter to the editor].Psychopharmacology,118, 118.

    Article  CAS  Google Scholar 

  • Ladewig, D. (1984). Dependence liability of the benzodiazepines.Drug and Alcohol Dependence,13, 139–149.

    Article  CAS  PubMed  Google Scholar 

  • Laegreid, L., Olegard, R., Wahlstrom, J., & Conradi, N. (1989). Teratogenic effects of benzodiazepine use during pregnancy.Journal of Pediatrics,114, 126–131.

    Article  CAS  PubMed  Google Scholar 

  • Lamb, R. J., & Griffiths, R. R. (1985). Effects of repeated Ro 15–1788 administration in benzodiazepine-dependentbaboons. European Journal of Pharmacology,110, 257–261.

    Article  CAS  Google Scholar 

  • Langtry, H. D., & Benfield, P. (1990). Zolpidem. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential.Drugs,40, 291–313.

    Article  CAS  PubMed  Google Scholar 

  • Levitan, E. S., Schofield, P. R., Burt, D. R., Rhee, L. M., Wisen, W., Kohler, M., Fujita, N., Rodriguez, H. F., Stephenson, A., Darlison, M. G., Barnard, E. A., & Seeburg, P. H. (1988). Structural and functional basis for GABA,A receptor heterogeneity.Nature(London), 335, 76–70.

    CAS  Google Scholar 

  • Livezey, G. T., Radulovacki, M., Isaac, L., Marczynski, T. J. (1985). Prenatal exposure to diazepam results in enduring reductions in brain receptors and deep slow wave sleep.Brain Research,334, 361–365.

    Article  CAS  PubMed  Google Scholar 

  • Lo, K. J., Eastwood, I. R., & Eidelman, S. (1967). Cholestatic jaundice associated with chlordiazepoxide hydrochloride (librium).American Journal of Digest Diseases,12, 845–849.

    Article  CAS  Google Scholar 

  • Longo, V. G., Massotti, M., DeMedici, D., & Valerio, A. (1988). Modifications of brain electrical activity after activation of the benzodiazepine receptor types in rats andrabbits. Pharmacology,Biochemistry and Behavior,29, 785–790.

    Article  CAS  Google Scholar 

  • Löscher, W., & Rundfeldt, C. (1989). Intermittent flumazenil and benzodiazepine tolerance: Discouraging findings in rats.Lancet,1, 1386.

    Article  PubMed  Google Scholar 

  • Lukas, S. E., & Griffiths, R. R. (1984). Precipitated diazepam withdrawal in baboons: Effects of dose and duration of diazepam exposure.European Journal of Pharmacology,100, 163–171.

    Article  CAS  PubMed  Google Scholar 

  • Macdonald, R. L., & McLean, M. J. (1986). Anticonvulsant drugs: Mechanisms of action.Advances in Neurology.44, 713–736.

    CAS  PubMed  Google Scholar 

  • Mandema, J. W., & Danhof, M. (1992). Electroencephalogram effect measures and relationships between pharmacokinetics and pharmacodynamics of centrally acting drugs.Clinical Pharmacokinetics,23, 191–215.

    Article  CAS  PubMed  Google Scholar 

  • Mandema, J. W., Sansom, L. N., Dios-Vièitez, M. C., Hollander-Jansen, M., & Danhof, M. (1991). Pharmacokinetic-pharmacodynamic modeling of the electroencephalographic effects of benzodiazepines. Correlation with receptor binding and anticonvulsant activity.Journal of Pharmacology and Experimental Therapeutics,257, 472–478.

    CAS  PubMed  Google Scholar 

  • Mandema, J. W., Kuck, M. T., & Danhof, M. (1992a). Differences in intrinsic efficacy of benzodiazepines are reflected in their concentration-EEG effect relationship.British Journal of Pharmacology,105, 164–170.

    Article  CAS  Google Scholar 

  • Mandema, J. W., Kuck, M. T., & Danhof, M. (1992b). In vivo modeling of the pharmacodynamic interaction between benzodiazepines which differ in intrinsic efficacy.Journal of Pharmacology and Experimental Therapeutics,26, 56–61.

    Google Scholar 

  • Mandema, J. W., Tukker, E., & Danhof, M. (1992). In vivo characterization of the pharmacodynamic interaction of a benzodiazepine agonist and antagonist: Midazolam and flumazenil.Journal of Pharmacology and Experimental Therapeutics,260, 36–44.

    CAS  PubMed  Google Scholar 

  • Manmaru, S., & Matsuura, M., (1990). Two kinds of spatiotemporal EEG changes after discontinuation of benzodiazepine, medazepam.Japanese Journal of Psychiatry and Neurology,44, 85–90.

    CAS  PubMed  Google Scholar 

  • Marquez-Orozco, A., Marquez-Orozco, M. C., & GazcaRamirez, M. V. (1993). Histological changes in the tibia of the mouse fetus exposed to diazepam.Proceedings of the Western Pharmacology Societu,36, 107–112.

    CAS  Google Scholar 

  • Marquez-Orozco, A., Hernandez-Alvarez, L. A. I., & Marquez-Orozco, M. C. (1994). Sexual activity in male mice treated prenatally with diazepam.Proceedings of the Western Pharmacology Society, 37, 65–68.

    CAS  PubMed  Google Scholar 

  • Marquez-Orozco, M. C., Marquez-Orozco, A., & GazcaRamirez, M. V. (1993). Effects of diazepam on the ultrastructure of fetal mice hepatocytes.Proceedings of the Western Pharmacology Society,36, 113–116.

    CAS  PubMed  Google Scholar 

  • Martin, J. R., & Haefely, W. E. (1995). Drugs used for the treatment of anxiety and sleep disorders. In P. L. Munson, R. A. Mueller, & G. R. Briese, (Eds.),Principles of pharmacology,basic concepts clinical practice(pp. 243–277 ). New York: Chapman & Hall.

    Google Scholar 

  • Martin, J. R., Moreau, J. L., & Jenck, F. (1995). Precipitated withdrawal in squirrel monkeys after repeated daily oral administration of alprazolam, diazepam, flunitrazepam or oxazepam.Psychopharmacology,118, 273–279.

    Article  CAS  PubMed  Google Scholar 

  • Martin, W. R., Sloan, J. W., & Wala, E. (1990). Precipitated abstinence in orally dosed benzodiazepinedependent dogs.Journal of Pharmacology and Experimental Therapeutics,255, 744–755.

    CAS  PubMed  Google Scholar 

  • Martin, W. R., Sloan, J. W., & Wala, E. P. (1993). Precipitated abstinence in the diazepam-dependent rat.Pharmacology,Biochemistry and Behavior,46, 683–688.

    Article  CAS  Google Scholar 

  • Martinez, J. A., Fargeas, M. J., & Bueno, L. (1992). Physical dependence on diazepam: Precipitation of abstinence syndromes by peripheral and central benzodiazepine receptor antagonists.Pharmacology,Biochemistry and Behavior,41, 461–464.

    Article  CAS  Google Scholar 

  • Massotti, M., Mele, L., & De Luca, C. (1990). Involvement of the “peripheral” benzodiazepine receptor type (ws) in the tolerance to the electroencephalographic effects of benzodiazepines in rats: Comparison of diazepam and clonazepam.Pharmacology. Biochemistry and Behavior,35, 933–936.

    Article  CAS  Google Scholar 

  • Mata-Santibanez, M. V., Marquez-Orozco, M. C., & Marquez-Orozco, A. (1993). Testicular histological changes in-mice after prenatal administration of diazepam.Proceedings of the Western Pharmacology Society,36, 177–121.

    Google Scholar 

  • Medina, J. H., Novas, M. L., & de Robertis, E. (1983). Chronic Ro 15–1788 treatment increases the number of benzodiazepine receptors in rat cerebral cortex and hippocampus.European Journal of Pharmacology,90, 125–128.

    Article  CAS  PubMed  Google Scholar 

  • Mele, L., Sagratella, S., & Massotti, M. (1984). Chronic administration of diazepam to rats causes changes in EEG patterns and in coupling between GABA receptors and benzodiazepine binding sites in vitro.Brain Research,323, 93–102.

    Article  CAS  PubMed  Google Scholar 

  • Mendelson, W. B. (1992). Neuropharmacology of sleep induction by benzodiazepines.Critical Reviews in Neurobiology,6, 221–232.

    CAS  PubMed  Google Scholar 

  • Mendelson, W. B., Gillin, J. C., & Wyatt, R. J. (1977).Human sleep and its disorders. New York: Plenum.

    Book  Google Scholar 

  • Miller, L G., & Koff, J. M. (1994). Interaction of central and peripheral benzodiazepine sites in benzodiazepine tolerance and discontinuation.Progress in Neuro-Ps.vchophu•maco[ogv Biological Psychiatry. 18, 847 - 857.

    Article  CAS  Google Scholar 

  • Miller, L. G., Greenblatt, D. J., Lopez, F., Schatzki, A., Heller, J., Lumpkin, M., & Shader, R. I. (1990). Chronic benzodiazepine administration: Effectsin vivoandin vitro. In G. Biggio & E. Costa (Eds.),GABA and benzodiazepine receptor subtypes(pp. 167–175 ). New York: Raven.

    Google Scholar 

  • Morrow, A. L., Pace, J. R., Purdy, R. H., & Paul, S. M. (1990). Characterization of steriod interactions with GABA receptor-gated chloride ion channels.Molecular Pharmacology,37. 262–270.

    Google Scholar 

  • National Institute on Drug Abuse. (1994a).Data from the Drug Abuse Warning Network (DAWN): Annual emergency room data 1992(NIDA Statistical Series I, No. 12-A, p. 37). Rockville, MD: Author.

    Google Scholar 

  • National Institute on Drug Abuse. (19946).Data from the Drug Abuse Warning Network (DAWN): Annual medical examiner data 1992 (NIDA Statistical Series I, No. 12-B, p. 21). Rockville, MD: Author.

    Google Scholar 

  • Nicoll, R. A. (1980). Sedative-hypnotics: Animal pharmacology. In L. L. Iversen, S. D. Iversen, & S. H. Snyder (Eds.),Handbook of psychopharmacology: Vol. 12. Drugs of abuse(pp. 187–234 ). New York: Plenum.

    Google Scholar 

  • Niddam, R., Dubois, A., Scatton, B., Arbilla, S., & Langer, S. Z. (1987). Autoradiographic localization of [3H]Zolpidem binding sites in the rat CNS: Comparison with the distribution of [3H]Flunitrazepam binding sites.Journal of Neurochemistry.49, 890–899.

    Article  CAS  PubMed  Google Scholar 

  • Norenberg, M. D., & Bender, A. S. (1994). Astrocyte swelling in liver failure: Role of glutamine and benzodiazepines.Acta Neurochirurgica 60, (Suppl.), 24 - 27.

    CAS  PubMed  Google Scholar 

  • Ober, K. (1974). Effects of diazepam on cell division rates and productivity ofSeenedesmus ohliguusin synchronous cultures.Archives of Microbiology,99, 369–378.

    Article  CAS  PubMed  Google Scholar 

  • Okamoto, M. (1978). Barbiturates and alcohol: Comparative overviews on neurophysiology and neurochemistry. In M. A. Lipton, A. DiMascio, & K. F. Killam (Eds.),Psychopharmacology: A generation of progress(pp. 1575–1590 ). New York: Raven.

    Google Scholar 

  • Persohn, E., Malherbe, P., & Richards, J. G. (1992). Comparative molecular neuroanatomy of cloned GABA, receptor subunits in the rat CNS.Journal of Comparative Neurology,326, 193–216.

    Article  CAS  PubMed  Google Scholar 

  • Pétursson, H. (1994). The benzodiazepine withdrawal syndrome.Addiction,89, 1455–1459.

    Article  PubMed  Google Scholar 

  • Pétursson, H., & Lader, M. H. (1981). Withdrawal from long-term benzodiazepine treatment.British Medical Journal,283, 643–645.

    Article  PubMed  Google Scholar 

  • Pole, P. (1988). Electrophysiology of benzodiazepine receptor ligands: Multiple mechanisms and sites of action.Progress in Neurobiology,31, 349–423.

    Article  Google Scholar 

  • Primus, R. J., & Gallager, D. W. (1992). GABA, receptor subunit mRNA levels are differentially influenced by chronic FG 7142 and diazepam exposure.European Journal of Pharmacology-Molecular Pharmacology Section,226, 21–28.

    Article  CAS  PubMed  Google Scholar 

  • Primus, R. J., Yu, J., Xu, J., Hartnett, M., Meyyappan, M., Kostas, C., Ramabhadran, T. V, & Gallager, D. W. (1996). Allosteric uncoupling after chronic benzodiazepine exposure of recombinant y-aminobutyric acids receptors expressed in Sf9 cells: Ligand efficacy and subtype selectivity.Journal of Pharmacology and Experimental Therapeutics.276, 882–890.

    CAS  PubMed  Google Scholar 

  • Pritchett, D. B.. Sontheimer, H.. Gorman, C. M., Kettenmann, H., Seeburg, P. H., & Schofield, P. R. (1988). Transient expression shows ligand gating and allostericpotentiation of GABA. receptor subunits.Science(Washington, DC),242, 1306–1308.

    Article  CAS  Google Scholar 

  • Regan, C. M., Gorman, A. M. C., Larsson, O. M., Maguire, C., Martin, M. L., Schousboe, A., & Williams, D. C. (1990).In vitro screening for anticonvulsant-induced teratogenesis in neural primary cultures and cell lines.International Journal of Developmental Neuroscience,8, 143–150.

    Google Scholar 

  • Rementeria, J. L., & Bhatt, K. (1977). Withdrawal symptoms in neonates from intrauterine exposure to diazepam.Journal of Pediatrics,90, 123–126.

    Article  CAS  PubMed  Google Scholar 

  • Richards, G., Möhler, H., & Haefely, W. (1986). Mapping benzodiazepine receptors in the CNS by radiohistochemistry and immunohistochemistry. In P. Panula, H. Paivarinta, & S. Soinila (Eds.),Neurohistochemistry: Modern methods and applications(pp. 629–677 ). New York: Liss.

    Google Scholar 

  • Richter, J. A., & Holtman, J. R., Jr. (1982). Barbiturates: Their in vivo effects and potential biochemical mechanisms.Progress in Neurobiology,18, 275–319.

    Article  CAS  PubMed  Google Scholar 

  • Rickels, K., Schweizer, E., Case, W. G., & Greenblatt, D. J. (1991). Long term therapeutic use of benzodiazepines: I. Effects of abrupt discontinuation.Archives of General Psychiatry,47, 899–907.

    Article  Google Scholar 

  • Robinson, R. L., Van Ryzin, R. J., Stoll, R. E., Jensen, R. D., & Bagdon, R. E. (1984). Chronic toxicity/carcinogenesis study of temazepam in mice and rats.Fundamentals and Applied Toxicology,4, 394–405.

    Article  Google Scholar 

  • Romach, M. K., Busto, U. E., Sobell, L. C., Sobell, M. B., Somer, M. A., & Sellers, E. M. (1991). Long-term alprazolam use: Abuse, dependence or treatment.Psychopharmacology Bulletin,27, 391–395.

    CAS  PubMed  Google Scholar 

  • Rosenberg, H. C. (1995). Differential expression of benzodiazepine anticonvulsant cross-tolerance according to time following flurazepam or diazepam treatment.Pharmacology,Biochemistry and Behavior,51, 363–368.

    Article  CAS  Google Scholar 

  • Rosenberg, H. C., & Chiu, T. H. (1982). An antagonist-induced benzodiazepine abstinence syndrome.European Journal of Pharmacology,81, 153–157.

    Article  CAS  PubMed  Google Scholar 

  • Roy-Byrne, P., Vittone, B. J., & Uhde, T. W. (1983). Alpra- zolam-related hepatotoxicity.Lancet,2, 786–787.

    Article  CAS  PubMed  Google Scholar 

  • Saano, V. (1993). Effects of peripherally acting benzodiazepines on cell growth and differentiation. In E. Giesen-Crouse (Ed.),Peripheral benzodiazepine receptors(pp. 1 I I-124). London: Academic Press.

    Google Scholar 

  • Sanger, D. J., Benavides, J., Perrault, G., Morel, E., Cohen, C., Joly, D., & Zivkovic, B. (1994). Recent developments in the behavioral pharmacology of benzodiazepine (w) receptors: Evidence for the functional significance of receptor subtypes.Neuroscience and Biobehavioral Reviews,18, 355–372.

    Article  CAS  PubMed  Google Scholar 

  • Sannerud, C. A., Cook, J. M., & Griffiths, R. R. (1989). Behavioral differentiation of benzodiazepine ligands after repeated administration in baboons.European Journal of Pharmacology,167, 333–343.

    Article  CAS  PubMed  Google Scholar 

  • Sassim, N., & Grohmann, R. (1988). Adverse drug reactions with clozapine and simultaneous application of benzodiazepines.Pharmacopsychiatry.21, 306–307.

    Article  CAS  PubMed  Google Scholar 

  • Saunders, P A., & Ho, I. K. (1990). Barbiturates and the GABAA receptor complex.Progress in Drug Research,34, 261–286.

    CAS  PubMed  Google Scholar 

  • Scherkl, R., & Frey, H. (1986). Physical dependence on clonazepam in dogs.Pharmacology,32, 18–24.

    Article  CAS  PubMed  Google Scholar 

  • Scheuler, W. (1990–1991). EEG sleep activities react topographically different to GABAergic sleep modulation by flunitrazepam: Relationship to regional distribution of benzodiazepine receptor subtypes?Neuropsychobiology,23, 213–221.

    Google Scholar 

  • Schlumpf, M., Parmar, R., Ramseier, H. R., & Lichtensteiger, W. (1990). Prenatal benzodiazepine immunosuppression: Possible involvement of peripheral benzodiazepine site.Developmental Pharmacology Therapeutics,15, 178–185.

    CAS  Google Scholar 

  • Schlumpf, M., Parmar, R., & Lichtensteiger, W. (1993). Prenatal diazepam induced persisting downregulation of peripheral (w3) benzodiazepine receptors on rat splenic macrophages.Life Sciences,52, 927–934.

    Article  CAS  PubMed  Google Scholar 

  • Schlumpf, M., Lichtensteiger, W, & van Loveren, H. (1994). Impaired host resistance toTrichinella spiralisas a consequence of prenatal treatment of rats with diazepam.Toxicology,94, 223–230.

    Article  CAS  PubMed  Google Scholar 

  • Schmidt, R. E, Vogel, M. E., & Zimmerman, M. (1967). Die wirkung von diazepam auf die präsynaptische hemmung and andere rückenmarksreflexe.NaunynSchmiedebergs Archives of Pharmacology,258, 69–82.

    Google Scholar 

  • Schofield, P. R., Darlison, M. G., Fugita, N., Burt, D. R., Stephenson, F. A., Rodriguez, H., Rhee, L. M., Ramachandran, J., Reale, V., Glencorse, T. A., Seeburg, P. H., & Barnard, E. A. (1987). Sequence and functional expression of the GABAA receptor shows a ligand-gated receptor super-family.Nature(London).328, 221–227.

    Google Scholar 

  • Shibuya, T., Watanabe, Y., Hill, H. E, & Salafsky, B. (1986). Developmental alterations in maturing rats caused by chronic prenatal and postnatal diazepam treatments.Japanese Journal of Pharmacology,40, 21–29.

    Article  CAS  PubMed  Google Scholar 

  • Sieghart, W. (1995). Structure and pharmacology ofyaminobutyric acid, receptor subtypes.Pharmacological Reviews,47, 181–234.

    CAS  PubMed  Google Scholar 

  • Sloan, J. W., Martin, W. R., & Wala, E. P. (1990). Dependence-producing properties of alprazolam in the dog.Pharmacology,Biochemistry and Behavior,35, 651–657.

    Article  CAS  Google Scholar 

  • Sloan, J. W., Martin, W. R., & Wala, E. P. (1991a). A comparison of the physical dependence inducing properties of flunitrazepam and diazepam.Pharmacology,Biochemistry and Behavior,39, 395–405.

    Article  CAS  Google Scholar 

  • Sloan, J. W., Martin, W. R., & Wala, E. (1991b). Duration of diazepam (DZ) treatment and the intensity of flumazenil precipitated abstinence (FPA) in dogs [Abstracts].Federation of the American Society for Experimental Biology Journal, 3, Part I, A703.

    Google Scholar 

  • Sloan, J. W., Martin, W. R., Wala, E., Dickey, K. M. (1991). Chronic administration of and dependence on halazepam, diazepam, and nordiazepam in the dog.Drug and Alcohol Dependence,28, 249–264.

    Article  CAS  PubMed  Google Scholar 

  • Sloan, J. W., Martin, W. R., & Wala, E. (1993a). Effect of the chronic dose of diazepam on the intensity and characteristics of the precipitated abstinence syndrome in the dog.Journal of Pharmacology and Experimental Therapeutics,265, 11–52.

    Google Scholar 

  • Sloan, J. W, Martin, W. R., & Wala, E. P. (1993b). Effects of flumazenil (F) and DMSO vehicle (V) microinjected (MI) into 4 brain sites in diazepam (D) dependent rats [Abstracts].Pharmacologist,35, 132.

    Google Scholar 

  • Sloan, J. W., Wala, E. P., & Jing, X. (1994). Comparison of the response of 4 hippocampal (H) sites in diazepam (DZ) dependent rats to flumazenil (F) microinjections.Society for Neuroscience Abstracts,20, 1604.

    Google Scholar 

  • Sloan, J. W., Wala, E. P., Jing, X., Holtman, J., Jr., & Lee, E. (1994). Chronic graded doses of diazepam capsule implants alter rat liver function tests [Abstracts].Federation of the American Society for Experimental Biology Journal, 8(4), Part I, 381.

    Google Scholar 

  • Sloan, J. W, Wala, E. P., & Jing, X. (1995a). Comparison of precipitated abstinence (PA) induced by focally injected flumazenil (FL) into different cerebellar (CB) loci in diazepam (DZ) dependent rats [Abstracts].Federation of the American Society for Experimental Biology Journal,9, A407.

    Google Scholar 

  • Sloan, J. W, Wala, E. P., & Jing, X. (19956). The effect of intra-amygdaloid administration of flumazenil in diazepam-dependent rats.Society for Neuroscience Abstracts,21, 2098.

    Google Scholar 

  • Sloan, J. W, Jing, X., Wala, E., & Milliken, B. (1996). The focal injection of flumazenil (FLU) into the CA, of hippocampus (Hi) of diazepam (DZ)-dependent rats produces a dose-related precipitated abstinence [Abstracts].Federation of the American Society for Experimental Biology Journal 10(3), A713.

    Google Scholar 

  • Sloan, J. W, Wala, E. P, & Jing, X. (1997a). PK 11195 (PK)-evoked withdrawal in diazepam (DZ)-dependent rats: Effect of dose of PK, DZ and gender.Neuroscience Abstracts,23(2), 2392.

    Google Scholar 

  • Sloan, J. W., Wala, E. P, & Jing, X. (1997b). The effect of focal injections of graded doses of flumazenil (FLU) and PK 11195 (PK) into the CAI of the hippocampus (HI) of diazepam (DZ)-dependent rats.Pharmacologist,39(1), 90.

    Google Scholar 

  • Smith, C. M. (1992). Antianxiety drugs. In C. M. Smith, & A. M. Reynard, (Eds.),Textbook of pharmacology(pp. 271–297 ). Philadelphia: Saunders.

    Google Scholar 

  • Speight, A. N. (1977). Floppy-infant syndrome and mater- nal diazepam and/or nitrazepam.Lancet,2, 878.

    Article  CAS  PubMed  Google Scholar 

  • Spivey, W. H. (1992). Flumazenil and seizures: Analysis of 43cases. Clinical Therapeutics,14, 292–305.

    CAS  Google Scholar 

  • Takeno, S., Hirano, Y., Kitamura, A., & Sakai, T. (1993). Comparative developmental toxicity and metabolism of nitrazepam in rats and mice.Toxicology Applied Pharmacology,121, 233–238.

    Article  CAS  Google Scholar 

  • Tedesco, F. J., & Mills, L. R. (1982). Diazepam (valium) hepatitis.Digestive Diseases and Sciences,27, 470–472.

    Article  CAS  PubMed  Google Scholar 

  • Thomson, I., Fraser, R., & Kenyon, C. J. (1995). Regulation of adrenocortical steroidogenesis by benzodiazepines.Journal of Steroid Biochemistry and Molecular Biology,53, 75–79.

    Article  CAS  PubMed  Google Scholar 

  • Tietz, E. I., Rosenberg, H. C., & Chiu, T. H. (1986). Autoradiographic localization of benzodiazepine receptor downregulation.Journal of Pharmacology and Experimental Therapeutics,236, 284–292.

    CAS  PubMed  Google Scholar 

  • Troisi, 1. 1., Jr., Critchfield, T. S., & Griffiths, R. R. (1993). Buspirone and lorazepam abuse liability in humans: Behavioral effects, subjective effects and choice.Behavioral Pharmacology,4, 217–230.

    Article  CAS  Google Scholar 

  • Tucker, J. C. (1985). Benzodiazepines and the developing rat: A critical review.Neuroscience and Biobehavioral Reviews,9, 101–111.

    Article  CAS  PubMed  Google Scholar 

  • Urbancic, M., Gadek, M. A., & Marczynski, T. J. (1990). Chronic exposure to flumazenil: Anxiolytic effect and increased exploratory behavior.Pharmacology,Biochemistry and Behavior,35, 503–509.

    Article  CAS  Google Scholar 

  • Valerio, A., & Massotti, M. (1988). Electroencephalographic changes after short-term exposure to agonists of benzodiazepine receptors in the rat.Pharmacology,Biochemistry and Behavior,29, 791–795.

    Article  CAS  Google Scholar 

  • Verdoorn, T. A. (1994). Formation of heteromericyaminobutyric acid type A receptors containing two different a subunits.Molecular Pharmacology,45, 475–480.

    CAS  PubMed  Google Scholar 

  • Verdoorn, T. A., Draguhn, A., Ymer, S., Seeburg, P. H., & Sakmann, B. (1990). Functional properties of recombinant rat GABAA receptors depend upon subunit composition.Neuron,4, 919–928.

    Article  CAS  PubMed  Google Scholar 

  • Wala, E. P., Sloan, J. W., & Jing, X. (1994). Intra-stratial administration of flumazenil (FL) to diazepam (DZ) dependent rats.Society for Neuroscience Abstracts 20, 1612.

    Google Scholar 

  • Wala, E. P, Sloan, J. W., Martin, W. R., & Jing, X. (1994) Abstinence syndrome following focal administrations of flumazenil (FL) into the cerebellum (CB) and fourth ventricle (4V) in diazepam (DZ) dependent rats.Canadian Journal of Physiology and Pharmacology,Abstracts XII International Congress of Pharmacology(Vol. 72, Suppl. 1 ), 391.

    Google Scholar 

  • Wala, E. P., Sloan, J. W, Jing, X., & Holtman, P. H. (1996). Intrathecally administed flumazenil and PK 11195 precipitate abstinence syndrome in diazepam dependent rats.Drug and Alcohol Dependence,43, 169–177.

    Article  CAS  PubMed  Google Scholar 

  • Wala, E. P, Sloan, J. W., & Jing, X. (1997a). Dorsal raphe and substantia nigra response to flumazenil in diazepam-dependent rats.Pharmacology,Biochemistry and Behavior,58(1), 221–229.

    Article  CAS  Google Scholar 

  • Wala, E. P., Sloan, J. W., & Jing, X. (1997b). Comparison of abstinence syndromes precipitated by flumazenil and PK 11195 in female diazepam-dependent rats.Psychopharmacology,133(3), 214–223.

    Article  CAS  Google Scholar 

  • Wala, E. P., Sloan, J. W., & Jing, X. (1997c). Substantia nigra: The involvement of the central and peripheral benzodiazepine receptors in physical dependence on diazepam in rats.Society for Neuroscience Abstracts,231(2), 2401.

    Google Scholar 

  • Weitzman, R., & Gavish, M. (1989). Chronic diazepam treatment induces an increase in peripheral benzodiazepine binding sites.Clinical Neuropharmacology,12, 346–351.

    Article  Google Scholar 

  • Weizman, R., Leschiner, S., Schlegel, W., & Gavish M. (1997). Peripheral-type benzodiazepine receptor ligands and serum steroid hormones.Brain Research,772, 203–308.

    Article  CAS  PubMed  Google Scholar 

  • Whitehouse, B. J. (1992). Benzodiazepines and steroidogenesis.Journal of Endocrinology 134, 1 - 3.

    Article  CAS  PubMed  Google Scholar 

  • Williams, M. (1984). Molecular aspects of the action of benzodiazepines and non-benzodiazepine anxiolytics: A hypothetical allosteric model of the benzodiazepine receptor complex.Progress in Neuro-Psychopharmacologv and Biological Psychiatry,8, 209–247.

    Article  CAS  Google Scholar 

  • Woods, J. H., Katz, J. L., & Winger, G. (1992). Benzodiazepines: Use, abuse, and consequences.Pharmacological Reviews,44, 151–347.

    CAS  PubMed  Google Scholar 

  • Yamadera, H., Kato, M., Ueno, T., Tsukahara, Y., & Okuma, T. (1993). Pharmaco-EEG mapping of diazepam effects using different references and absolute and relative power.Pharmacopsychiatry,26, 254–258.

    Article  CAS  PubMed  Google Scholar 

  • Yanagita, T. (1981). Dependence-producing effects of anxiolytics. In F. Hoffmeister & G. Stille (Eds.),Psychotropic agents(pp. 395–406 ). Berlin: Springer-Verlag.

    Chapter  Google Scholar 

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Sloan, J.W., Wala, E.P. (1998). Pharmacology of Sedatives, Hypnotics, and Anxiolytics. In: Tarter, R.E., Ammerman, R.T., Ott, P.J. (eds) Handbook of Substance Abuse. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-2913-9_27

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