Radioreceptor binding technique as aid in treatment with neuroleptics
In all medicinal treatment efforts must be made to find the optimal dose for each patient separately. Both therapeutic effects and adverse effects may occur at doses differing widely from one individual to another. Furthermore, the use of a given dose of a drug may perhaps result in the blood concentration of the drug being anything up to 30 times higher in one patient than in another (Hammer and Sjöqvist, 1967; Forsman and Öhman, 1975; Axelsson and Mårtensson, 1976). It is possible to ascertain the optimal dosage level or range of several drugs, that is the dose producing a maximum effect with a minimum of side effects. By adjusting the dose of a drug according to its concentration in the serum, for example, it has proved possible to improve the effect of the drug and to minimize its side effects. But it has so far not been possible to establish a generally applicable concentration range for neuroleptics. This failure has been ascribed, first, to the fact that most neuroleptics are transformed to a series of active metabolites. One can therefore not a priori expect the clinical picture to vary solely with the blood concentration of the drug, which is only one of the active substances. Second, it has become increasingly clear that the response to a given concentration can vary from one patient to another. As far as neuroleptics are concerned, this variation may be due to a probably genetic variation of the susceptibility of the dopamine (DA) system.
KeywordsHigh Performance Liquid Chromatography Active Metabolite Concentration Of70 Radioreceptor Assay Prolactin Response
Unable to display preview. Download preview PDF.
- Axelsson, R., Forsman, A., Wendestam, C. and Öhman, R. (1980). A biomathematical model for prolactin response to dopamine blocking agents in man. Manuscript.Google Scholar
- Fink, M. (1978). Eeg effects of clozapine: association or dissociation of eeg and behaviour? In Neuropsychopharmacology. Proceedings of the 11th Congress of the Collegium International Neuropsychopharmacologicum, Vienna, 1978 (ed. B. Saletu, P. Berner and L. Hollister), Pergamon Press, OxfordGoogle Scholar
- Forsman, A. and Larsson, M. (1978). Metabolism of haloperidol. Curr. Ther. Res., 24, 567–8Google Scholar
- Forsman, A., Larsson, M. and Öhman, R. (1980). A high-performance liquid chromatographic method for the determination of haloperidol and reduced haloperidol in serum. J. Chromatogr., submittedGoogle Scholar
- Forsman, A. and Öhman, R. (1975). Some aspects on the distribution and metabolism of haloperidol in man. In Antipsychotic Drugs, Pharmacokinetics and Pharmacodynamics (ed. G. Sedvall), Pergamon Press, Oxford and New YorkGoogle Scholar
- Hammer, W. and Sjöqvist, F. (1967). Plasma levels of monomethylated tricyclic antidepressants during treatment with imipramine-like compounds. Life Sci., 122, 301–10Google Scholar
- Hays, S., Poland, R. and Rubin, R. (1980). Prolactin releasing potencies of antipsychotic and related non-antipsychotic compounds in female rats: relation to clinical potencies. J. Pharmac. exp. Ther., in pressGoogle Scholar