Methods to Facilitate Early Exploratory Testing of Novel Psychopharmacologic Agents in Humans
The starting point for this chapter follows from three assumptions: (1) substantial numbers of patients seriously ill with psychiatric illnesses such as schizophrenia and depression show inadequate therapeutic responses to all available classes of drugs; (2) decisions to take new potential psychotropic compounds into humans are more and more based on judgments as to the likelihood of there being a reasonable market for that specific compound; and (3) pharmacologic guidance can greatly enhance the efficiency of the clinical development process both in terms of reducing wasted effort in Phase I testing and of deriving maximum information concerning the appropriate dose to test the therapeutic potential of a novel compound. With regard to this latter point, it is well known that even marketed psychotropic drugs have had very misleading dose recommendations because what is required for marketing is to establish safe doses which on average have a positive effect rather than doses which produce the maximum possible benefit.
KeywordsToxicity Dopamine Schizophrenia Marketing Cocaine
Unable to display preview. Download preview PDF.
- Collins JM, Zaharko DS, Dedrick RL, Chabner BA (1986) Potential roles for preclinical pharmacology in phase 1 clinical trials. Cancer Treat Rev 70: 73–80Google Scholar
- Dreyfus JF, Cremniter D, Guelfi JD (1989) Reflections on FDA and WHO recommendations concerning clinical trials. Psychiatry Psychobiol 4: 117–122Google Scholar
- Osman OT, Potter WZ (1991) Potentiation of dopamine in the treatment of refractory depression. In: Amsterdam JD (ed) Refractory depression. Raven, New York, p 41 (Advances in neuropsychiatry and psychopharmacology, vol 2 )Google Scholar
- Paalzow LK, Paalzow GHM, Tfelt-Hansen P (1985) Variability in bioavailability: concentration versus effect. In: Rowland M et al. (eds) Variability in drug therapy: description, estimation, and control. Raven, New York, p 167Google Scholar
- Peck C (1990) The randomized concentration-controlled clinical trial (CCT): an information-rich alternative to the randomized placebo-controlled clinical trial (PCT). Clin Pharmacol Ther 47 (2): 148Google Scholar
- Peck C, Collins J, Harter J (1990) Incorporation of pharmacokinetic and pharmacodynamic intelligence into early drug development. Clin Pharmacol Ther 47 (2): 126Google Scholar
- Posvar EL, Sedman AJ (1989) New drugs: first-time in man. J Clin Pharmacol 19: 961–966Google Scholar
- Salvadorini F, Galeone F, Saba P, Tognetti G, Mariani G (1980) Evaluation of S-adenosylmethionine (SAMe) effectiveness on depression. Curr Ther Res 27 (6): 908–918Google Scholar
- Sansone M (1978) Effects of S-adenysyl-L-methionine on the behavior of mice. In: Andreoli VM, Agnoli A, Fazio C (eds) Transmethylations and the central nervous system. Springer, Berlin Heidelberg New York, p 121Google Scholar
- Sheiner LB (1985) Modeling pharmacodynamics: parametric and nonparametric approaches. In: Rowland M et al. (eds) Variability in drug therapy: description, estimation, and control. Raven, New York, pp 139–152Google Scholar
- Sjoerdsma A, Lovenberg W, Engelman K, Carpenter WT, Wyatt RJ, Gessa GL (1970) Serotonin now: clinical implications of inhibiting its synthesis with parachlorophenylalanine. J Intern Med 73: 607–629Google Scholar