Tioridazin - ett atypiskt neuroleptikum? Översikt över farmakodynamiska effekter av tioridazin och dess huvudmetaboliter

Despite its clinical use for more than two decades, many intriguing questions remain about the pharmacology of thioridazine. As has been eloquently reviewed by Carlsson (26), many cellular loci may play a role in the antipsychotic actions of thioridazine and its active metabolites. The data we have presented demonstrate that mesoridazine and sulforidazine are much more potent in various functional tests of antidopaminergic potency than would have been expected from radioligand binding assays. However, no evidence was found from either psychopharmacological or biochemical studies for selectivity of mesolimbic versus striatal dopamine receptors of either the parent drug or the metabolites. The significance of these data are heightened by recent findings that the selective dopamine D, antagonist SCH23390 is extremely potent at blocking psychopharmacological effects previously believed to be D₂ in nature (31). Although this drug is almost certainly relatively selective for dopamine receptors (32), it causes its psychopharmacological effects without the concomitant changes of neuronal firing, neurotransmitter turnover, or release caused by other dopamine receptor blockers. It was more than two decades ago that Carlsson and Lindqvist (27) provided evidence that dopamine receptor blockade is a critical aspect of antipsychotic drug action, yet we are still far from a clear understanding of these systems. Further studies with thioridazine and its metabolites will have to be made, paying attention to these basic advances. It does seem clear that a better understanding of how the available drugs act, and techniques to optimize their use, are likely to be one consequence of research efforts in this area. ? Thioridazine, metabolites, pharmacodynamics.