From Animal Experiments to Clinical Dosing: Some Aspects of Preclinical Development of Antidepressants

  • A. Delini-Stula
Conference paper
Part of the Psychopharmacology Series book series (PSYCHOPHARM, volume 7)


In the preclinical evaluation of new drugs several questions must be answered before a drug can be released for administration to humans. Obviously, the first question is always: Does the drug possess the desired pharmacological activity at all? If such activity is identified, there are other important questions which may be answered only in more elaborate studies. During the various phases of preclinical evaluation of a new drug (Table 1) the potency and dose dependency of effects, general and specific toxicity, its relationship to the desired activity, and additional pharmacological effects and their relation to the main effect must be established. The findings generated in each phase of preclinical studies determined the decision as to further development of the drug for a particular indication. In other words, the pharmacological objectives of drug research in animals consist of the evaluation of the profile and mechanism of action and thus the prediction of the therapeutic properties, efficacy and side effect profile of a drug.


Side Effect Profile Preclinical Evaluation Noradrenaline Uptake Behavioural Despair Antidepressant Potential 


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  1. Beckmann H, Goodwin FK (1975) Antidepressant response to tricyclics and urinary MHPG in unipolar patients. Clinical response to imipramine or amitriptyline. Arch Gen Psychiatry 32(1): 17–21Google Scholar
  2. Bowden CL, Davis J, Garver DL, Hanin I, Koslow S, Maas JW (1987) Changes in urinary catecholamines and their metabolites in depressed patients treated with amitriptyline or imipramine. J Psychiatry Res 21 (2): 111–128Google Scholar
  3. Charney DS, Heniger GR, Steinberg DE, Roth RH (1981) Plasma MHPG in depression: effects of acute and chronic desipramine treatment. Psychiatry 5(2): 217–229Google Scholar
  4. Delini-Stula A (1983) Pharmakologie der Antidepressiva. In: Langer G, Heimann H (eds) Psychopharmaka - Grundlagen und Therapie. Springer, Vienna New York, pp 81–95Google Scholar
  5. Delini-Stula A (1986) New pharmacological findings in depression. Psychopathology 19 [Suppl 2]: 94–102Google Scholar
  6. Delini-Stula A, Hauser K, Baumann P, Olpe HR, Waldmeier PC, Storni A (1982) Stereospecificity of behavioural and biochemical response to oxaprotiline - a new antidepressant. Adv Biochem Psychopharmacol 31: 265–275PubMedGoogle Scholar
  7. Delini-Stula A, Vassout A, Hauser K, Bittiger H, Büch O, Olpe HR (1983) Oxaprotiline and its enantiomers: do they open new avenues in the research of the mode of action of antidepressants? In: Usdin E, Goldstein M, Friedhoff A, Georgotas A (eds) Frontiers in neuropsychiatric research. Mcmillan, London, pp 121–134Google Scholar
  8. Flament MF, Rapoport IL, Murphy DL, Berg CJ, Lake CR (1987) Biochemical changes during clomipramine treatment of childhood, obsessive-compulsive disorder. Arch Gen Psychiatry 44(3): 219–225Google Scholar
  9. Lingjaerde D (1980) Antidepressants and serotonin uptake in platelets. Acta Psychiatr Scand [Suppl 280] 61: 111–119Google Scholar
  10. Maitre L, Moser P, Baumann PA, Waldmeier PC (1980) Amine uptake inhibitors: criteria of selectivity. Acta Psychiatr Scand [Suppl 280] 61: 97–l10Google Scholar
  11. Maitre L, Baumann P, Jaekel J, Waldmeier PC (1982) 5-HT uptake inhibitors: psycho- pharmacological and neurobiological criteria of selectivity. Adv Biochem Psychopharmacol 34: 229–246Google Scholar
  12. McKinney WT, Bunney WE (1969) Animal models of depression. Arch Gen Psychiatry 21: 240–248PubMedGoogle Scholar
  13. Mishra R, Gillespie DD, Lovell R, Robson RD, Sulser F (1982) Oxaprotiline: induction of central noradrenergic subsensitivity by its (+)-enantiomer. Life Sci 30: 1747–1755PubMedCrossRefGoogle Scholar
  14. Porsolt RD (1981) Behavioural despair. In: Enna SJ et al. (eds) Antidepressants: neurochemical, behavioural and clinical perspectives. Raven, New York, pp 121–139Google Scholar
  15. Waldmeier PC, Baumann PA, Hauser K, Maitre L, Storni A (1982) Oxaprotiline, a noradrenaline uptake inhibitor with an active and an inactive enantiomer. Biochem Pharmacol 31: 2163–2176CrossRefGoogle Scholar
  16. Wendt G, (in press) Levoprotiline-clinical antidepressive efficacy and tolerability. Neuropharmacology, Proceedings of the XYIth CINP Congress, Munich 1988Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • A. Delini-Stula
    • 1
  1. 1.Research and DevelopmentCiba-Geigy Ltd.BaselSwitzerland

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