Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Some recent research on the behavioural effects of phenylethylamine and some recent data implicating the trace amines in schizophrenia, agoraphobia and aggression are briefly outlined. 2. Phenylethylamine produces in mice a distinctive hyperactivity syndrome consisting of two phases; it appears to act via dopamine and 5-hydroxytryptamine on different components of these stereotypies. 3. Urinary unconjugated tryptamine, and meta- and para-tyramine appear to be excreted in reduced amounts in schizophrenia and bipolar depression. 4. The blood levels of the trace acids phenylacetic and meta- and para-hydroxyphenylacetic are reduced in schizophrenia. 5. Blood levels of conjugated phenylacetic and unconjugated para-hydroxyphenylacetic acid are reduced in violent as opposed to non-violent offenders. 6. The neuromodulatory role of the trace amines and their possible involvement in components of behaviour and certain mental disorders are discussed.
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PMID:Some aspects of basic psychopharmacology: the trace amines. 629 92

Risperidone, a benzisoxazol derivative, is a novel antipsychotic agent which combines potent serotonin (5-hydroxytryptamine) 5-HT2 and dopamine D2 receptor antagonism. Development of the drug was stimulated by reports that the selective serotonin 5-HT2 antagonist ritanserin improved the negative symptoms of schizophrenia and decreased extrapyramidal symptoms when combined with haloperidol. The relatively low incidence of extrapyramidal symptoms with risperidone may reflect a preferential action on mesolimbic rather than nigrostriatal dopaminergic pathways. Recent clinical investigation suggests that risperidone is of at least comparable efficacy to haloperidol and perphenazine in improving the symptoms of acute and chronic schizophrenia on short term administration. Advantages offered by risperidone over haloperidol include a faster onset of antipsychotic action, a lower incidence of extrapyramidal effects and possibly greater efficacy against the negative symptoms of schizophrenia. If these benefits prove to be maintained during long term therapy, risperidone is likely to make a significant contribution to the treatment of schizophrenia.
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PMID:Risperidone. A review of its pharmacology and therapeutic potential in the treatment of schizophrenia. 752 27

It has been suggested that changes in brain 5-hydroxytryptamine3 receptor function may contribute to some behavior disorders, such as anxiety, schizophrenia and drug abuse. We are using the whole-cell version of the patch-clamp technique to study the function of 5-hydroxytryptamine3 channels in neurons freshly dissociated from rat nodose ganglion. In these cells, 5-hydroxytryptamine elicits an inward current over the concentration range of 0.25-100 microM (EC50 = 2.62 microM) by activating 5-hydroxytryptamine3 receptors. The muscarinic cholinergic antagonist atropine reduced the amplitude of 5-hydroxytryptamine activated inward current in a concentration-dependent manner. Other muscarinic antagonists, scopolamine, dexetimide, the M1 muscarinic receptor antagonist pirenzepine, the M2 receptor antagonist methoctramine and the M3 receptor antagonist 4-DAMP methiodide also inhibited 5-hydroxytryptamine-induced inward current. Atropine did not appear to change the reversal potential of this current. In the presence of 5 microM atropine, the concentration-response curve for 5-hydroxytryptamine current was shifted to the right in a parallel fashion. The EC50 value for 5-hydroxytryptamine was increased from 2.62 to 8.76 microM. Schild plots of increasing atropine and 5-hydroxytryptamine concentrations revealed a pA2 value of 5.74 for atropine (apparent KD = 1.8 microM). These observations suggest that atropine competitively antagonizes the activation of a receptor for the neurotransmitter serotonin, a novel action of muscarinic antagonists in the nervous system. This effect of atropine may contribute to the clinical symptoms seen in severe atropine intoxication.
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PMID:The effect of atropine on the activation of 5-hydroxytryptamine3 channels in rat nodose ganglion neurons. 753 5

By the use of positron emission tomography (PET), high central dopamine D2 receptor occupancy (70 to 90%) has been demonstrated in patients treated with conventional neuroleptics. In patients treated with the atypical antipsychotic clozapine, the D2 occupancy was low (20 to 67%). The effects of clozapine may thus be mediated by a mechanism distinct from D2 occupancy. The observation that low doses of clozapine (125 to 175 mg daily) induced more than 80% (5-hydroxytryptamine) 5-HT2 occupancy supports the view that 5-HT2 antagonism may be related to the atypical effects of clozapine. Risperidone is a new antipsychotic drug with high affinity in vitro for both central 5-HT2 and D2 receptors. In this study, we determined the D2 and 5-HT2 occupancy induced by clinical treatment with risperidone. Four patients with acute exacerbation of schizophrenia were examined by PET after 4 weeks of treatment with risperidone, 6 mg daily. The D2 occupancy in the striatum was 75 to 80%. The 5-HT2 occupancy in the neocortex was 78 to 88%. This study confirms that, in patients with schizophrenia, treatment with risperidone induces a high D2 and 5-HT2 occupancy. Risperidone is, accordingly, a suitable drug for the examination of the clinical benefit of combined serotonin and dopamine antagonism.
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PMID:Positron emission tomography studies on D2 and 5-HT2 receptor binding in risperidone-treated schizophrenic patients. 753 84

Serotonin (5-hydroxytryptamine, 5-HT) receptors as well as dopamine receptors are important in connection with schizophrenia. In this study we evaluated the effects of the 5-HT1A receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT) and 5-HT1B receptor agonist (1-(3-trifluoromethylphenyl)piperazine, TFMPP) on the single and paired rats' movement distance in an open-field. Generally animals are gregarious in their natural setting, so the presence of another companion might alter the effects of the drugs. Therefore we devised a video analysis system to pick up the two rats' movements individually through two CCD video cameras and objectively recorded two rats' movement for 30 minutes. Experimental rats were injected with 8-OH-DPAT (0.05, 0.25, 1.25, 6.25 mg/kg, s.c.) or TFMPP (0.12, 0.5, 2.0, 8.0 mg/kg, i.p.) and the control rats were injected with saline. In the single cases experiments, the rats were put alone into the open field after the injection. In the paired cases experiments, they were put into the open field with a companion rat after the injection. In the 8-OH-DPAT experiment, the movement distance of single cases showed dose dependent increase tendency and that of the 1.25 mg/kg group and the 6.25 mg/kg group showed significant increase, but that of paired cases did not show that tendency, on the contrary, the movement distance of 0.05 mg/kg group showed significant decrease. In the TFMPP experiment, the movement distance of 2.0 mg/kg groups showed significant increases in the single and the paired cases. These findings suggest that both 5-HT1A receptors and 5-HT1B receptors affect the rats' movement distance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of 5-HT1A receptor agonist and 5-HT1B receptor agonist on single and paired rats' behavior]. 754 36

Conventional neuroleptics are widely accepted as being effective against the positive symptoms of schizophrenia, but do not benefit all patients. Furthermore, they are relatively ineffective against negative symptoms and cognitive disorders, and most have unpleasant side effect profiles. New strategies for treating schizophrenia include the development of dopamine antagonists with high selectivity for different subtypes of dopamine receptors, dopamine partial agonists, antagonists at different serotonin (5-hydroxytryptamine; 5-HT) receptor subtypes, drugs with mixed pharmacological profiles and drugs which modify transmission via amino acids or peptides in the brain. The prospect is that some of these strategies will lead to the introduction of new drugs and that some of these will become the standards against which future drugs will be compared. The search for new drugs and their use in clinical practice will also lead to developments in our knowledge and understanding of schizophrenia.
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PMID:New drugs for the treatment of schizophrenic patients. 760 35

After four decades of the use of antipsychotic drugs that target the dopamine D2 receptor as the initial site of action, a new strategy for antipsychotic therapy has emerged and, with it, new hope for greater efficacy and fewer side effects. This new strategy involves identifying drugs with strong serotonin (5-hydroxytryptamine) 5-HT2A receptor relative to dopamine D2 receptor blocking properties. Clozapine is now known to have these properties, but risperidone is the first drug to be designed intentionally to have these properties. Others are being developed. These drugs, the serotonin-dopamine antagonists (SDAs), may prove to have many other uses in psychiatry beyond schizophrenia because of their low propensity to cause extrapyramidal symptoms. Their pharmacologic mechanism of action may be more complex than only strong 5-HT2A and weak D2 block, e.g., 5-HT2C and D4 receptor blockade. Nevertheless, the SDAs are proving to be valuable tools in the analysis of both normal brain function and the etiology of schizophrenia.
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PMID:The role of serotonin in schizophrenia and the place of serotonin-dopamine antagonist antipsychotics. 773 Apr 97

Serotonin (5-hydroxytryptamine; 5-HT) has been implicated in a large number of psychophysiologic processes including the regulation of sleep, appetite, mood, aggression, perception, memory, and anxiety. To mediate this large array of physiologic processes, at least 14 separate 5-HT receptors have evolved, which are divided into seven main families. Not surprisingly, alterations of 5-HT receptor activity have been shown to occur in many psychiatric diseases including anxiety, depression, eating disorders, schizophrenia, personality disorders, and many drug-induced psychotic states. Additionally, a number of effective psychopharmacologic agents for diseases as diverse as schizophrenia and anxiety have been developed which either specifically alter brain levels of serotonin or bind to 5-HT receptor subtypes. This review article summarizes recent advances in the burgeoning field of serotonin receptor pharmacology and integrates this information into a coherent perspective on the importance of serotonergic agents for clinical psychiatry.
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PMID:Multiple serotonin receptors: clinical and experimental aspects. 780 91

This article reviews current knowledge on the interaction between 5-hydroxytryptamine (5-HT), acting at 5-HT3 receptors in the CNS, and cerebral dopamine systems. Since 1987, a growing body of behavioural, neurochemical and electrophysiological evidence from animal studies has demonstrated a clear role for 5-HT3 receptors in the modulation of activity of mesolimbic and mesocortical dopamine neurones. This evidence has led to the suggestion that 5-HT3 receptor antagonists have potential as novel antipsychotic agents and may also find use in the treatment of psychoactive substance abuse. Data emerging from clinical studies generally support this hypothesis and suggest that 5-HT3 antagonists may prove to be among the first agents available to treat schizophrenia which are not dopamine D2 antagonists and hence lack their side-effect problems.
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PMID:Interactions between 5-HT3 receptors and cerebral dopamine function: implications for the treatment of schizophrenia and psychoactive substance abuse. 783 43

Progress toward understanding the role of the 5-hydroxytryptamine (5-HT)2 receptor in the therapy for schizophrenia has been hampered by the lack of highly selective antagonists. We now report on the effects of MDL 100,907 [R(+)-alpha-(2,3-dimethoxyphenyl)-1- [2-(4-fluorophenylethyl)]-4-piperidine-methanol], a highly selective and potent 5-HT2 receptor antagonist, in behavioral, electrophysiological and neurochemical models of antipsychotic activity and extrapyramidal side-effect liability. In mice, MDL 100,907 blocked amphetamine-stimulated locomotion at doses that did not significantly affect apomorphine-stimulated climbing behavior. Neither MDL 100,907 nor clozapine reduced apomorphine-induced stereotypies or produced catalepsy in rats. MDL 100,907 blocked the slowing of ventral tegmental area (A10) dopaminergic neurons by amphetamine but, like clozapine, produced only small increases in the number of active substantia nigra zona compacta (A9) and A10 dopamine neurons after acute administration. When administered chronically, MDL 100,907 and clozapine selectively reduced the number of spontaneously active A10 neurons, whereas haloperidol reduced activity in both the A9 and A10 regions. Consistent with their acute effect on A9 and A10 activity, neither MDL 100,907 nor clozapine increased dopamine metabolism in the striatum or nucleus accumbens, whereas acute haloperidol accelerated dopamine turnover in both regions. The administration of the dopamine uptake blocker amfonelic acid with haloperidol produced a massive increase in DA metabolism characteristic of typical antipsychotics. In contrast, MDL 100,907 and clozapine were without effect on dopamine turnover when given in the presence of amfonelic acid. These data indicate that MDL 100,907 has a clozapine-like profile of potential antipsychotic activity with low extrapyramidal sid-effect liability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of the 5-HT2 receptor antagonist MDL 100907 as a putative atypical antipsychotic: behavioral, electrophysiological and neurochemical studies. 810 46


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