[Development of new antipsychotic drugs].
As far as schizophrenia is concerned, therapeutical effects of neuroleptics based on brain-located dopamine receptor blockers are taken for granted. It is also admitted, however, that classical neuroleptics have inconveniences, namely: Their relative lack of effect on negative symptoms, and their liability to induce extrapyramidal symptoms (EPS). Pipamperone-based clinical studies evidenced that an antagonist combining serotonin 5-HT2, and dopamine D2 was successful in the treatment of schizophrenia--which could be clearly observed in (a) anti-autistic effects, (b) regulating disrupted sleep-wake rhythms, and (c) a lesser tendency to EPS. Setoperone-based studies--a compound with a comparable pharmacological profile--confirmed the above observations. Until, however, the synthesis of ritanserin--a specific, and selective antagonistic receptor--was not achieved, no exact implication of 5-HT2 antagonist in psychopharmacological treatments of schizophrenia could be explored further. Indeed, double-blind trials evidenced a remarkable improvement in negative as well as extrapyramidal symptoms. Since a monotherapy appeared as undeniably called for in the treatment of schizophrenia, the next logical step to be taken was selecting a compound with a central antagonism comparable to ritanserin's, and a central D2 antagonism comparable to haloperidol's. Among a chemical range of benzisoxazole derivatives, risperidone was thus selected. The first double-blind trials on chronic schizophrenic patients seem indeed to confirm that this substance is likely to get over the above mentioned inconveniences, so typical of classical neuroleptics.
Vanden Bussche
G
G
Clinical Research and Development Department, Janssen Research Foundation, Beerse, Bélgica.
Gelders
Y G
YG
Heylen
S L
SL
D002090:Butyrophenones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D011744:Pyrimidinones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D016713:Ritanserin; D012559:Schizophrenia / Q000188:drug therapy*; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D012890:Sleep / Q000187:drug effects*
D002090:Butyrophenones; D010880:Piperidines; D011744:Pyrimidinones; D012702:Serotonin Antagonists; D016713:Ritanserin; C005569:pipamperone; C045359:setoperone
El desarrollo de nuevas drogas antipsicóticas.