Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-15T07:29:12.151Z Has data issue: false hasContentIssue false

The prospects of new antipsychotic principles

Published online by Cambridge University Press:  18 September 2015

Extract

Biological schizophrenia research has been dominated by the dopamine hypothesis for decades, but in recent years a more diversified view has gained increasing attention. Several neurotransmitters are now being discussed, and especially their interaction in complex circuitries.

The demonstration of an atypical profile of clozapine (Leponex®), with lessened extrapyramidal side effects and somewhat increased efficacy, has stimulated this research field considerably. This agent has high affinity not only for the different dopamine receptor subtypes, but also for serotonergic, alpha-adrenergic and muscarinic receptors. Different workers have stressed one or more of these sites as being of major importance for the atypical profile of clozapine, and several drug companies have made attempts to mimic the profile of clozapine by developing molecules with affinity for these receptors in varying proportions. A number of such agents have reached or will soon reach the market and appear to be promising, even though they may not match clozapine in terms of atypicality.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1997

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Literature

1.Carlsson, A. The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacol 1988;1:179–86.CrossRefGoogle ScholarPubMed
2.Carlsson, M, Carlsson, A. The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice. J neural Transm 1989;75: 221–6.CrossRefGoogle ScholarPubMed
3.Svensson, A, Carlsson, ML. Injection of the competitive NMDA receptor antagonist AP-5 into the nucleus accumbens of monoamine-depleted mice induces pronounced locomotor stimulation. Neuropharmacol 1992;31:513–8.CrossRefGoogle ScholarPubMed
4.Carlsson, M, Carlsson, A. Interactions between glutamatergic and mono- aminergic systems within the basal ganglia-implications for schizophrenia and Parkinson's disease. Trends Neurosci 1990;13: 272–6.CrossRefGoogle Scholar
5.Hansson, LO, Waters, N, Winblad, B, et al.Evidence for biochemical heterogeneity in schizophrenia: a multivariate study of mono-aminergic indices in human post-mortem brain tissue. J neural Transm [GenSect] 1994;98:217–35.CrossRefGoogle Scholar
6.Kornhuber, HH, Kornhuber, J, Kim, JS, et al.Zur biochemischen Theorie der Schizophrenie. Nervenarzt 1984;55:602–6.Google Scholar
7.Garland Bunney, B, Bunney, WE, Carlsson, A. Schizophrenia and glutamate. In: Bloom, FE, Kupfer, DJ, eds. Psychopharmacology: The Fourth Generation of Progress. New York: Raven Press 1995;1205–13.Google Scholar
8.Lahti, A, Weiler, MA, Corey, PK, et al.Treatment of schizophrenia: New antidopaminergic strategies. Biol Psychiat 1996;39: 597.CrossRefGoogle Scholar