Serotonin 5-HT2 receptor antagonists - Potential in the treatment of psychiatric disorders

This review highlights recent pharmacological and clinical advances in the understanding of the potential use of serotonin 5-HT2 receptor antagonists as treatments for a number of psychiatric disorders, namely anxiety, depression and schizophrenia. 5-HT2 receptor antagonists have not vet been clearly demonstrated to be effective in humans as treatments for anxiety, Some preliminary clinical trials suggest that the 5-HT2 receptor antagonist ritanserin may have a beneficial effect in patients with generalised anxiety disorder, but the evidence is far from compelling. Upregulation of central 5-HT2 receptors anti an accompanying increase in phosphoinositide turnover appear to be predisposing biological factors in depression. A functional interaction between 5-HT1A and 5-HT2 receptors mac be of particular importance, since 5-HT2 receptor antagonism can ultimately result in a facilitation of 5-HT1A receptor-mediated neurotransmission and this may be beneficial for the treatment of depression, Ritanserin appears to be more effective than placebo in alleviating the depressive symptoms of dysthymia. Nefazodone is a nets antidepressant that combines 5-HT2 receptor blockade with serotonin reuptake inhibition, Comparisons with imipramine favour nefazodone in terms of tolerability and suggest that both drugs are equally clinical effective, In schizophrenia, 5-HT2A receptor function appears to be altered. Modulation of dopaminergic function via 5-HT2A receptors may provide a viable mechanism for enhancing the effect of antipsychotics. Risperidone, the first post-clozapine agent that has 5-HT2A and dopamine D-2 receptor antagonist actions, is at least as effective as haloperidol and perphenazine in reducing acute psychotic symptoms. Its major clinical advantages are a greater efficacy in controlling the secondary negative symptoms and a lower incidence of extrapyramidal symptoms (EPS). The efficacy of ritanserin in alleviating both positive and negative symptoms in acutely psychotic patients stems to support thr hypothesis that potent 5-HT2A receptor antagonism alone may contribute to the therapeutic action of several clinically effective antipsychotics that have reduced liability to induce EPS.