| Abstract: | A sizeable number of new chemical entities designed to effectively treat acute and chronic schizophrenic behaviour have been disclosed in the patent literature during 1995 and 1996 and are discussed in this update. While the majority of these cases involve compounds which display high affinity for CNS dopamine receptors (particularly D2 and D4 subtypes), many others claim the ability to produce efficacy through indirect regulation of dopaminergic activity, e.g., via serotonin selective mechanisms. Still others offer the possibility of relief through interactions with less obvious receptors including neurokinin, glutamate and nicotinic systems. Many of these inventions also claim the potential for clozapine-like ‘atypical’ profiles, but with the advantage of being free from the potential for inducing blood disorders, like agranulocytosis, which could limit market exposure of a commercial product. The gradual emergence and success of new antipsychotic drugs, including risperidone, which combine potent dopamine and serotonin receptor selectivities in a single compound, demonstrate the advances possible in the pharmacotherapy of schizophrenia, but equally highlights the shortcomings (e.g., extrapyramidal side-effects [EPS] liability, ineffective treatment of refractory/non-responsive population) still to be adequately addressed. |
