Psychiatric disorders, treatment Antagonists

Eplivanserin (39) is a 5-HT2A antagonist initially developed for a broader spectrum of psychiatric disorders but that has been tested recently for insomnia. Within this latter indication, phase II studies showed benefits in sleep maintenance, but not in induction [9]. Compound 39 is currently in phase III, to assess the efficacy for the treatment of sleep maintenance insomnia, evaluating both sleep and daytime functioning [96]. 

The early suggestion by Fozard [54] that 5-HT3 receptor antagonists may be useful in the treatment of migraine has yet to be established, although MDL 72222 appeared to be effective in limited clinical trials [94, 95]. There are exciting prospects for other clinical applications of 5-HT3 antagonists in psychiatric disorders which have been predicted from behavioural studies in rodents and primates, and several clinical trials are underway in psychiatric patients. 

The part played by endogenous opioid systems in the regulation of these various physiological and behavioral functions has led to the experimental application of opiate antagonists in psychiatric disorders. This chapter focuses on autism and self-injury, which are two potential indications for opiate antagonists in pediatric populations. In adults, treatment with opiate antagonists has shown to be useful in the relapse prevention of alcoholism as part of a comprehensive treatment approach (Anton et ah, 1999, 2001). 

Dopamine is a major neurotransmitter which acts on multiple receptors. It can activate both a and 3 adrenoceptors in addition to acting on specific dopamine receptors. These are widely distributed throughout the CNS and are also present in the renal tubules and renal and mesentric blood vessels, and many dopaminergic drugs are used in the treatment of Parkinson s disease, psychiatric disorders, as antiemetics, and for renal protection. Neuroleptic drugs, such as haloperidol and droperidol, are dopamine receptor antagonists. 

Psychiatric Disorders. The main indications for DA antagonists are the treatment of adult schizophrenia, and childhood psychosis. Haloperidol and chlorpromazine are the most frequently employed. 

M. H.Eader, The Role of Ondansetron, a Novel 5HT3 Antagonist, in the Treatment of Psychiatric Disorders (Satellite Symposium 5th World Congress Biological Psychiatry), 1991, pp. 17-19. 

HT2-type receptors have been a focus for investigations into its putative clinical importance for treatment of psychiatric disorders. h-HTg-type receptors have been implicated in several disorders like anxiety, depression and psychosis. As we are presently in the dark with respect to the mechanisms underlying the development of these disorders, future pharmacotherapy largely aims at alleviating symptoms. To that end various compounds, which have antagonistic properties on S-HTj-type receptors, are currently tested in clinical studies. 

Based on the erroneous notion that mental illness and seizure disorders were antagonistic, psychiatrists induced seizures as a treatment for depression and other psychiatric problems. Convulsive therapy was first described clinically by Ladislas J. Meduna. In 1934, he injected camphor liniment to induce seizures in patients with schizophrenia, some of whom actually improved. His technique was recognized immediately for its therapeutic value and adopted worldwide within a few years of its introduction. Other chemicals, such as metronidazole (Metrozol), were administered under the mistaken hehef that such treatments would consistently reheve the symptoms of mental illness. Pharmaco-convulsive therapy frightened patients and was fiuught with shortcomings, such as the unreliable induction of seizures. 

Anxiety and depression are psychiatric disorders that constitute a major health problem throughout world. While numerous marketed treatments exist for both disorders, there remains a continuing need for drugs with increased efficacy and/or reduced side-effect profiles [164,165]. CRF (1) receptor antagonists have been proposed as novel pharmacological treatments for depression, anxiety and stress disorders [164-166]. 

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