Serotonin Receptors and Antipsychotic Drug Action
The effect of serotonin (5-HT) to modulate dopaminergic activity in the nigrostriatal system has been known for some time (Dray et al. 1976). Generally, 5-HT has an inhibitory effect on dopaminergic output (see Meltzer and Nash 1991, for review). However, there is also evidence that 5-HT can enhance some aspects of dopaminergic function; thus, an over-simplistic one-way model should not be considered (Meltzer and Nash 1991). The effect of 5-HT in modulating dopaminergic activity is mediated via specific 5-HT receptors, the nature of which will be discussed subsequently. Due to the central role that antagonism of dopamine (DA) receptors has in the ability of antipsychotic drugs to reduce psychotic symptoms and in producing side effects such as extrapyramidal symptoms, tardive dyskinesia, and stimulation of prolactin secretion (Meltzer and Stahl 1976), it is necessary to consider whether serotonergic influences modulate the action of at least some antipsychotic drugs. As will be discussed, it has been suggested that serotonergic effects are particularly relevant to the action of clozapine and some other so-called atypical antipsychotic drugs (see Meltzer 1989; Deutch et al. 1991, for reviews). This article will consider the evidence for the action of antipsychotic drugs on specific 5-HT receptors as a contributing factor to their antipsychotic action or unique side effect profile.
KeywordsDopamine Schizophrenia Prolactin Haloperidol Nash
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- Bersani G, Grispini A, Marini S, Pasini A, Valducci M, Ciani N (1986) Neuroleptic-induced extrapyramidal side effects: clinical perspectives with ritanserin (R35667), a new selective 5-HT2 receptor blocking agent. Curr Ther Res 40: 492–499Google Scholar
- Farde L, Wiesel FA, Nordstrom A-L, Sedvall G (1989) D1- and D2-dopamine receptor occupancy during treatment with conventional and atypical neuroleptics. Psychopharmacology (Berl) 99 Suppl:S-28–S-31Google Scholar
- Meltzer HY (1988) Clozapine: clinical advantages and biological mechanisms. In: Schulz C, Tamminga C (eds) Schizophrenia: a scientific focus. International conference on schizophrenia. Oxford University Press, New York, pp 302–309Google Scholar
- Meltzer HY (1990b) The role of serotonin in the action of atypical antipsychotic drugs. Psychiatr Ann 20 (10): 571–579Google Scholar
- Meltzer HY, Stockmeier CA (1992) The influence of 5-HT2/5-HT1c receptor blockade on the action of clozapine and other Type A atypical antipsychotic drugs. Br J Psychiatry (in press)Google Scholar
- Meltzer HY, Alphs LD, Bastani B, Ramirez L (1989a) Effect of melperone in treatment resistant schizophrenia (Abstr). Excerpta Med Int Congr Ser 889: 502Google Scholar
- Meltzer HY, Zhang Y, Stockmeier CA (1990) Effect of typical and atypical antipsychotic drugs (APD) on frontal cortical (FC), serotonin2 (5-HT2) and striatal (STR) dopamine2 (DA2) binding in vivo. Neurosci Abstr 16: 586Google Scholar
- Mertens C, Dewilds J, Dierick M, Bergman I, Gustavsson G (1989) Clinical trials of amperozide in schizophrenia (Abstr). Excerpta Med Int Congr Ser 889: 502Google Scholar
- Yagaloff KA, Hartig GR (1985) 125I-lysergic acid diethylamide binds to a novel serotonergic site on rat choroid plexus epithelial alls. J Neurosci 5:3718–3183Google Scholar