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)

This study sought to determine whether depressive symptoms and/or platelet serotonin receptor (5HT2A) density are associated with increased platelet activation (PA) found among smokers. Flow cytometric detection of PA was used to study 36 smokers and 16 nonsmokers, aged 18 to 48 years. Subjects were tested at baseline and after either smoking 2 cigarettes (smokers) or a similar resting interval (nonsmokers). Assessment of PA included both platelet secretion and fibrinogen receptor (GPIIb/IIIa) binding. Platelet 5HT2A receptor binding and saturation were tested using [3H]LSD, and depressive symptoms were measured using the Beck Depression Inventory. Platelet 5HT2A receptor density was increased among smokers versus nonsmokers (82.7+/-67.7 versus 40.0+/-20.2 fmol/mg protein; P<0.005), and there was a dose-dependent relationship between receptor density and packs/d among smokers. Baseline wound-induced GPIIb/IIIa binding at 1 minute and GPIIb/IIIa binding in response to collagen stimulation in vitro was increased among smokers (P<0.05); there were no changes in PA among smokers after smoking, and platelet secretion was not elevated among smokers. Depressive symptoms were associated with 5HT2A receptor density among nonsmokers (P<0.005), but no such relationship was evident among smokers; PA was unrelated to 5HT2A receptor density in either group. The findings indicate that smoking is associated with increased platelet serotonin receptor density and with increased GPIIb/IIIa receptor binding, although these 2 factors are not related to each other or to depressive symptoms among smokers. Serotonergic dysfunction may be an important factor in the development of cardiovascular disease among smokers.
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PMID:Increased serotonin receptor density and platelet GPIIb/IIIa activation among smokers. 1007 84

Serotonin selective reuptake inhibitors (SSRIs) are currently among the most frequently prescribed therapeutic agents in all of medicine. Their therapeutic actions are diverse, ranging from efficacy in depression to obsessive-compulsive disorder, panic disorder, bulimia and other conditions as well. The plethora of biological substrates, receptors and pathways for serotonin are candidates to mediate not only the therapeutic actions of SSRIs, but also their side effects. Specifically, the immediate actions of SSRIs are mostly side effects, and may be mediated by the initiating actions of SSRIs, namely negative allosteric modulation of the serotonin transporter. A leading hypothesis to explain these immediate side effects is that serotonin is increased at specific serotonin receptor subtypes in discrete regions of the body where the relevant physiologic processes are regulated. Desensitization of post-synaptic receptors in these same discrete brain regions may explain the development of tolerance to these same side effects. The explanation for therapeutic effects characteristic of SSRIs may be found in delayed neurochemical adaptations. A leading hypothesis for this action is desensitization of somatodendritic serotonin 1A autoreceptors in the midbrain raphe. The hypothesis to explain why SSRIs have such diverse therapeutic actions is that somatodendritic 5HT1A autoreceptor desensitization increases serotonin in those critical brain regions and at those key serotonin receptor subtype(s) which may mediate the pathophysiologies of the various disorders. Understanding the topography of serotonin receptor subtypes in discrete anatomical pathways may enhance our understanding of both the therapeutic actions and side effects of these important pharmaceutical agents.
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PMID:Mechanism of action of serotonin selective reuptake inhibitors. Serotonin receptors and pathways mediate therapeutic effects and side effects. 1033 79

Within 3 h of ingesting an imbalanced amino acid diet (Imb), rats show attenuated intake, which can be ameliorated by prior administration of the serotonin receptor antagonist tropisetron (Trop). Earlier work in which the dorsomedial hypothalamic nucleus (DMN) was electrolytically lesioned (DMNL) determined that this structure plays a role in the early detection of and subsequent adaptation to Imb. However, that study did not address whether cell bodies in the DMN, fibers of passage, or both were involved in the DMNL response to Imb. In the present investigation in experiment 1, rats were given electrolytic DMNL or a sham operation (Sham). The rats were injected with saline (Sal) or Trop just before introduction of Imb. By 3 h Sal-DMNL rats consumed more Imb than did the Sal-Sham rats; intake was normal by 12 h. Trop enhanced Imb intake, with Trop and DMNL being additive. By day 4 the DMNL rats were eating and gaining weight less than were Sham rats. In experiment 2, DMN cell bodies were destroyed by ibotenic acid (Ibo). Sal-injected Ibo-lesioned and Sham rats showed similar food intake depression on Imb; Trop similarly increased Imb intake in both groups. By day 4 both Ibo-L rats were eating and gaining weight less than were Sham rats. In experiment 3, groups of rats were given knife cuts posterior, lateral, ventral, dorsal, or anterior to the DMN. During the first 3 h of consuming Imb, all cuts except posterior enhanced the intake of Imb. Over the next 24 h the anterior cut group continued to eat more Imb than did the Sham rats. In experiment 4 DMNL rats were given novel diets; the DMNL rats did not display a neophilic response. The data suggest that fiber tracts that pass through the DMN may be involved in the early detection of Imb. DMN cell bodies, or fibers of passage, are not involved in the Trop effect. Finally, DMN cell bodies are necessary for proper long-term adaptation to Imb.
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PMID:Effects of dorsomedial hypothalamic nuclei lesions on intake of an imbalanced amino acid diet. 1040 80

The serotonin receptor type 2A (5-HT2A) is a primary candidate for involvement in major psychoses. Polymorphisms within the 5-HT2A gene have recently been reported to be associated with a variety of psychopathological conditions. In the present study, we investigated the potential influence of the T102C polymorphism on the psychopathology of schizophrenia. One hundred eighty-eight inpatients affected by schizophrenia (DSM-III-R) were assessed by the Operational Criteria checklist for psychotic illness (OPCRIT) and were typed for their 5-HT2A variants by PCR techniques. Mania, depression, delusion and disorganization were the four symptomatologic factors previously derived from our psychotic population that were used to define phenotype in our sample. Genetic variants of the polymorphism under study were not associated with these symptomatologic factors, and consideration of possible stratification effects such as sex and age of onset did not reveal any association either. Our results do not, therefore, support the hypothesis that the serotonin receptor 2A gene is a liability factor for the symptomatology of schizophrenia as defined by the OPCRIT checklist. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:84-87, 2000.
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PMID:Serotonin-2A receptor gene is not associated with symptomatology of schizophrenia. 1068 58

Serotonin 5-HT(1A) receptor antagonists potentiate the effects of serotonin reuptake inhibitors on extracellular serotonin levels in a variety of brain regions. These effects are quite variable, however, with reports indicating potentiations of anywhere from 100-1900%. One factor that might impact the magnitude of such potentiations is the timing of administration of the two agents; reports in which the reuptake inhibitor is given prior to the serotonin receptor antagonist consistently report larger potentiations than reports in which the antagonist is given first. To test this relationship directly, microdialysis and electrophysiology studies were performed to assess the magnitude of increase in extracellular serotonin and changes in cellular activity produced by the serotonin reuptake inhibitor fluoxetine and the 5-HT(1A) receptor antagonist WAY-100635 under various dosing regimens. In microdialysis studies, when WAY-100635 (0.5 mg/kg s.c.) was administered 80 min after fluoxetine (10 mg/kg i.p.) the increase in serotonin was more than twice that observed when the compounds were coadministered. In electrophysiology studies in vivo, WAY-100635 reversed the depression of cell firing produced by fluoxetine when administered 30 min after fluoxetine, but when the two compounds were coadministered, a depression in firing rate was observed comparable to that produced by fluoxetine alone. In contrast, slice recording studies showed that WAY-100635 blocked the effects of fluoxetine regardless of the order of administration. These results indicate that fluoxetine and WAY-100635 can interact in a fashion not predicted by the currently accepted model. It is likely that neuronal circuitry outside of the raphe nuclei underlies this relationship.
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PMID:Differential effects of coadministration of fluoxetine and WAY-100635 on serotonergic neurotransmission in vivo: sensitivity to sequence of injections. 1094 Nov 37

This article reviews how to establish the diagnosis of migraine, the possible differential diagnoses, and the present state of the art of therapy. Emphasis is laid on nonsteroidal antiphlogistic drugs, serotonin receptor agonists (the so called triptans), and antiemetic drugs. The interval therapy consists of beta-blockers, calcium antagonists, antiepileptics, and serotonin receptor antagonists. The pathophysiology is based on the concept of sterile neurogenic inflammation, cortical spreading depression (CSD), and hyperexcitability of the central nervous system (CNS).
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PMID:Therapy of Migraine Headache in Cancer Patients. 1099 76

Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter involved in a number of physiological functions including sleep, appetite, pain perception, and sexual activity. Several pathological states such as migraine, depression, and anxiety have been linked to the serotonergic system, and serotonergic drugs have been used to treat these disorders. To date, there are 14 known serotonin receptor subtypes through which serotonin exerts its multiple actions. The classic pharmacological approach to study how these individual receptor subtypes contribute to various behaviours has been to use selective drugs that either block or activate certain receptor subtypes, and then study the effects of these compounds on physiology and behaviour. A complementary genetic approach is the technique of gene targeting. Using this technology, we and others have begun to examine the contribution of several serotonin receptor subtypes to complex behaviours through the generation of knockout mice that lack the genes encoding these receptors. In this review, we will describe what we have learned about the serotonergic system and the function of the 5-HT(1B) receptor by the analysis of 5-HT(1B) receptor knockout mice. Furthermore, we will discuss the implications of these findings and our plans for future studies.
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PMID:Knockout Corner. 1128 82

Hypericum perforatum is considered an effective alternative to the synthetic antidepressants in the treatment of mild-to-moderate depression. Recently, we showed that the effects on neurotransmitter contents in different brain regions of laboratory animals are more evident after administration of hypericum extracts containing a higher concentration of flavonoids, thus suggesting that these compounds are important in the antidepressant action of hypericum perforatum. We studied the effects of Ph-50, a hypericum extract standardized to flavonoids (50%) and containing 0.3% hypericin and 4.5% hyperforin on brain serotonin content, norepinephrine and dopamine by a high-performance liquid chromatography method in discrete brain areas (cortex, diencephalon and brainstem) in male Sprague-Dawley rats. Moreover, we evaluated the effects of Ph-50 alone or in association with sulpiride (a dopamine receptor antagonist), metergoline (a serotonin receptor antagonist) and 6-hydroxydopamine (6-OH-DA, destroying norepinephrine-containing neurons) using a forced-swimming test in the rat. Hypericum extract (Ph-50; 250-500 mg/kg) with acute oral administration enhanced serotonin, norepinephrine and dopamine content in the brain and reduced the immobility time of rats in the forced-swimming test. Sulpiride, metergoline and 6-OH-DA significantly increased the period of immobility in the forced-swimming test for the rats receiving hypericum extract (Ph-50). The results indicate that the neurotransmitters studied could be involved in the anti-immobility effects of hypericum, and suggest that its antidepressant action is probably mediated by serotonergic, noradrenergic and dopaminergic system activation.
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PMID:Serotonin, norepinephrine and dopamine involvement in the antidepressant action of hypericum perforatum. 1130 63

Anxiety and depressive disorders share many features, suggesting a common set of physiologic substrates. Recent research has indicated that mood can be categorized into 3 components by factor analysis: (1) somatic anxiety (a factor relatively specific to panic disorder), (2) anhedonic depression (which includes symptoms related to motivation and enjoyment and found to be specific to depression), and (3) general distress (a factor that cuts across all depressive and anxiety disorders studied). Antidepressant drugs, particularly serotonin reuptake inhibitors and serotonin receptor modulators, are effective for a wide variety of anxiety and depressive disorders. The impact on both anxiety and depression may be a result of an effect on a common set of physiologic targets relevant to the general distress dimension. At a cellular level, the antidepressants target components of the stress-adaptation system in brain, which may explain these common effects. On the other hand, there appear to be differences in the relative impact of serotonergic and noradrenergic drugs on the spectrum of distress and motivational symptoms. Basic research and clinical research suggest that serotonergic agents may be preferentially effective for symptoms of general distress, whereas catecholaminergic agents may target anhedonic depression symptoms.
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PMID:Mechanisms of action in the treatment of anxiety. 1143 Jun 13

Ziprasidone is a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. The initial evidence suggests an effective dosage range of 80-160 mg/day. Clinical trials suggest that the drug is an effective antipsychotic in schizophrenia and schizoaffective disorder with a beneficial effect on negative symptoms and symptoms of depression. The main adverse effects appear to be somnolence (14%) and nausea (10%). Ziprasidone has relatively fewer side-effects and yet has at least equivalent efficacy for florid 'positive' symptoms compared with conventional antipsychotics. The additional serotonergic actions deliver further efficacy against 'negative' and affective symptoms of schizophrenia. Reduced effects on cognitive abilities compared to conventional antipsychotics make ziprasidone more attractive still. Barring any unforeseen complications, it appears to a most valuable addition to the antipsychotic agents.
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PMID:Focus on ziprasidone. 1175 85


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