Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antipsychotic drug risperidone shows high affinity for both central serotonin (5-HT)2A and dopamine (DA)-D2 receptors in vivo. By employing microdialysis in freely moving rats, the effects of acute risperidone administration on regional brain DA and 5-HT release and metabolism were compared with the corresponding effects of the atypical antipsychotic drug clozapine as well as amperozide, the selective DA-D2 receptor antagonist raclopride and the selective 5-HT2A/5-HT2C receptor antagonist ritanserin. Risperidone (0.2 or 2.0 mg/kg, SC) was found to increase DA release and metabolism to about the same extent in three major projection areas of the mesotelencephalic dopaminergic system, i.e. the nucleus accumbens (NAC), the medial prefrontal cortex (MPC) and the lateral striatum (STR). In contrast, clozapine and amperozide (both 10.0 mg/kg, SC), as well as raclopride (2.0 mg/kg, SC), were all found differentially to affect DA release and metabolism in the three projections areas. Specifically, clozapine and amperozide enhanced DA release in the MPC to a greater extent than in the NAC or the STR, whereas raclopride instead preferentially increased DA release in the NAC and the STR but not in the MPC. Ritanserin (3.0 mg/kg, SC) did not exert any major effects on DA metabolism in the three areas studied. In contrast to the regionally rather homogenous activation of brain DA systems caused by risperidone, the drug was found to enhance brain 5-HT metabolism preferentially in the MPC, as indicated by the elevated extracellular concentration of 5-hydroxyindoleacetic acid (5-HIAA) in this region. A similar elevation of the 5-HIAA level in the MPC was observed after amperozide and, to some extent, after clozapine and ritanserin administration. The risperidone-induced (2.0 mg/kg, SC) elevation of 5-HIAA concentrations in the frontal cortex was found to be paralleled by an increased 5-HT release in this brain area. Consequently, our findings demonstrate a pharmacological profile of risperidone, as reflected in brain DA metabolism, in between that of clozapine and the DA-D2 antagonists. The preferential activation of 5-HT release and metabolism in frontal cortical areas might be of particular relevance for the ameliorating effect of risperidone on negative symptoms in schizophrenia, especially when associated with depression.
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PMID:Risperidone: regional effects in vivo on release and metabolism of dopamine and serotonin in the rat brain. 893 2

Parallel effects of a single injection of the 5-HT(2) receptor antagonist ritanserin on EEG power spectra, sleep and motor activity were measured for a 20-h period in freely moving Sprague-Dawley rats. Ritanserin (0.3 mg/kg, i.p.), administered at light onset (passive phase), caused an immediate transient increase in the EEG power density in the low frequency range (0.25-6 Hz, mainly delta activity) and a depression in the high frequency range (27-30 Hz) accompanied by a decrease in vigilance and light slow wave sleep (SWS-1), intermediate stage of sleep and increase in deep slow wave sleep (SWS-2) compared to control treatment. All these effects were over 8 h after the injection. Twelve hours after the injection, at dark onset (active phase), there was a marked increase in vigilance and motor activity and decrease in SWS-1 and spindle frequency activity in the control animals, but all these changes were diminished by ritanserin treatment. These effects resulted in a significant relative increase in the intermediate band (peak: 12-15 Hz) of the EEG power spectra and thus, a relative increase in thalamo-cortical synchronization caused by ritanserin at dark onset. Because ritanserin is a selective 5-HT(2) receptor antagonist, we conclude that under physiological conditions serotonin increases EEG desynchronization and produces an increase in vigilance level and motor activity by tonic activation of 5-HT(2) receptors. This regulatory mechanism plays an important role in the waking process, and the appearances of its effects in the light and dark phase are markedly different.
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PMID:Acute and long-term effects of the 5-HT2 receptor antagonist ritanserin on EEG power spectra, motor activity, and sleep: changes at the light-dark phase shift. 1208 44

A preclinical evaluation is presented of the serotonin 5-HT2 antagonists ritanserin and risperidone. Whereas ritanserin is a relative selective 5-HT2 antagonist, risperidone is a potent 5-HT2 and catecholamine antagonist. The pharmacological differences between both drugs are also observed in the drug discrimination test procedure. Using DOM, d-amphetamine and cocaine. Ritanserin was found active in animal models of anxiety using natural aversive stimuli; and in animal models of depression. Clear differences were observed between ritanserin and the benzodiazepines and between ritanserin and the tricyclic antidepressants. Risperidone was active in animal models of psychosis. Risperidone has, as opposed to classical neuroleptics such as haloperidol, less risks of inducing a dopamine D2 overblockade. Clinically, ritanserin is described as a thymostenic agent. Risperidone is an antipsychotic with therapeutic effects on both the positive and negative symptoms of schizophrenia and with a reduced risk of extrapyramidal side-effects.
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PMID:Central 5-HT2 antagonists: A preclinical evaluation of a therapeutic potential. 2695 56


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