Preclinical Pharmacodynamics of Central Nervous System Active Agents
In preclinical drug development power spectral analysis of drug induced changes in the electroencephalogram (EEG) is often used to characterize the pharmacological properties of new psychotropic drugs. In this chapter a new approach is proposed for this type of investigations, which allows additional quantitative pharmacodynamic information (i.e. potency, intrinsic efficacy, rate of biophase equilibration) to be derived.
KeywordsPsychotropic Drug Small Laboratory Animal Unit Impulse Response Intrinsic Efficacy Sigmoidal Emax Model
Unable to display preview. Download preview PDF.
- Bowery, N. G. (1982). Baclofen: 10 years on. Trends Pharmacol.Sci.Oct 400–403.Google Scholar
- Faigle, J. W., H. Keberle, and P. H. Degen (1980). Chemistry and pharmacokinetics of baclophen. In R. G. Feldman, R. R. Young, and W. P. Koella (Eds.), Spasticity: Disordered Motor Control. Year Book Medical Publishers, Chicago, pp 461–475.Google Scholar
- Haefely, W., E. Kyburz, M. Gerecke, and H. Mohler (1985). Recent advances in the molecular pharmacology of benzodiazepine receptors and in the structure activity relationships of their agonists and antagonists. Adv. Drug Res.14 165–322.Google Scholar
- Haefely, W., L. Pieri, P. Polc, and R. Schaffner (1981). General pharmacology and neuropharmacology of benzodiazepine derivatives. In F. Hoffmeister and G. Stille (Eds.), Handbook of Experimental Pharmacology. Vol. 55/II Springer, Berlin, pp 13–262.Google Scholar
- Herrmann, W. M. (1982). Development and critical evaluation of an objective procedure for the electroencephalographic classification of psychotropic drugs. In W. M. Heinnann (Ed.), Electroencephalography in Drug Research Gustav Fisher Verlag, Stuttgart, pp. 249–351.Google Scholar
- Itil, T. M. (1974a). Digital computer analyzed EEG in psychiatry and psychopharmacology. In G. Dolce and H. Kunkel (Eds.), CEAN Computerized EEG Analysis Gustav Fischer Verlag, Stuttgart, pp. 289–308.Google Scholar
- Itil, T. M. (1974b). Quantitative pharmaco-electroencephalography. Use of computerized cerebral biopotentials in psychotropic drugs. In T. M. Itil, (Ed.), Modern Problems in Pharmacopsychiatry. Vol. 8: Psychotropic Drugs and the Human EEG Karger, Basel, pp. 43–75.Google Scholar
- Itil, T. M. (1981). The discovery of psychotropic drugs by computer-analyzed cerebral bioelecric potentials (CEEG). Drug Development Research 1, 373–407.Google Scholar
- Mandema, J. W., L. N. Sansom, M. M. C. Dios-Vietez, M. Hollander-Jansen, and M. Danhof (1991b). Pharmacokinetic-pharmacodynamic modelling of the electroencephalographic effects of benzodiazepines. Correlation with receptor binding and anticonvulsant activity. J. Pharmacol. Exp. Ther. 257 472–478.Google Scholar
- Mandema, J. W., E. Tukker, and M. Danhof (1992b). In vivo characterization of the pharmacodynamic interaction of a benzodiazepine agonist and antagonist: midazolam and flumazenil. J. Pharmacol.Exp. Ther., 261 56–61Google Scholar
- Mandema, J. W., C. D. Heijligers-Feijen, E. Tukker, A. G. de Boer, and M. Danhof (1992c). Modeling of the effect site equilibration kinetics and pharmacodynamies of racemic baclofen and its enantiomers using quantitative EEG measures. J. Pharmacol Exp. Ther., 261 88–95.Google Scholar