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

Methysergide, a congener of LSD and potent serotonin (5-HT) antagonist, induced a florid transient psychosis resembling an LSD psychosis in a patient with spasmodic torticollis with a family history of schizophrenia. Thirteen years later he developed a major depression. A variety of other drug challenges and treatments for his torticollis had no psychotomimetic effect. Blockade of 5-HT receptors may subserve methysergide-induced psychosis.
 ...
PMID:Methysergide-induced psychosis: case report with long-term follow-up. 248 59

The effect of systemic administration of ritanserin (R 55667), a 5-hydroxytryptamine (5-HT2) receptor antagonist, on midbrain dopamine (DA) neurons was studied with single cell recording techniques in the chloral hydrate anesthetized male rat. Dopamine cells of the zona compacta, substantia nigra (ZC-SN) and the ventral tegmental area (VTA) were identified by established criteria. Ritanserin (0.5-2.0 mg/kg, IV) dose-dependently increased both the burst firing and firing rate of the midbrain DA neurons. These effects were prevented by endogenous 5-HT depletion through pretreatment with the 5-HT synthesis inhibitor para-chlorophenylalanine (PCPA, 300 mg/kg, IP, x3), which did not significantly alter the firing characteristics of the midbrain DA cells when given alone. These results suggest that 5-HT exerts an inhibitory control of midbrain DA cell activity mediated by 5-HT2 receptors. The stimulatory effect of ritanserin on midbrain DA systems might contribute to some of its clinical effects, such as improvement of mood, drive and motivation as well as its therapeutic actions in parkinsonism and type II schizophrenia.
 ...
PMID:Ritanserin, a 5-HT2 receptor antagonist, activates midbrain dopamine neurons by blocking serotonergic inhibition. 252 59

Clozapine can produce greater clinical improvement in both positive and negative symptoms than typical antipsychotic drugs in neuroleptic-resistant schizophrenic patients. The clinical response may occur rapidly in some patients but is delayed in others. Clozapine has also been reported to produce fewer parkinsonian symptoms, to involve a lower risk of producing tardive dyskinesia, and to produce no serum prolactin elevations in man. It seems likely that these effects are the result of a common biological mechanism or related mechanisms, rather than unrelated effects. Other atypical antipsychotic drugs, such as melperone and fluperlapine, share at least some of these properties. A relatively low affinity for the D-2 dopamine (DA) receptor and high affinity for the 5-HT2 receptor, producing a high 5-HT2/D-2 ratio, best distinguishes atypical antipsychotics like clozapine from typical antipsychotic drugs. Through its weak antagonist action on D-2DA receptors and a potent inhibitory effect on 5-HT2 receptors, as well as its ability to increase DA and 5-HT2 release, clozapine may be able to permit more normal dopaminergic function in the anterior pituitary, the mesostriatal, mesolimbic and mesocortical regions. The numerous advantages of clozapine over typical neuroleptics are consistent with the primary importance of DA to the pathophysiology of schizophrenia. The secondary but still significant role of 5-HT in the action of clozapine may either be direct or via the effect of 5-HT on dopaminergic mechanisms. Some aspects of schizophrenia could be due to a dysregulation of the interaction between serotonergic and dopaminergic neurotransmission.
 ...
PMID:Clozapine: new research on efficacy and mechanism of action. 256 75

Clozapine administration to schizophrenic patients was found to produce dopamine2 (D-2) and serotonin2 (5-HT2) receptor blockade, as evidenced by the ability to block the increases in growth hormone and cortisol secretion produced by apomorphine and MK-212, respectively, direct acting dopamine (DA) and 5-HT2 agonists. Clozapine did not increase plasma prolactin (PRL) levels nor did it block the apomorphine-induced decrease in plasma PRL concentration, as would be expected from a D-2 receptor antagonist. These PRL results are consistent with the observation that clozapine may increase DA release. Clozapine also decreased plasma tryptophan, plasma homovanillac acid (HVA) and basal plasma cortisol levels. Rodent studies suggest clozapine also increases 5-HT release. We hypothesize that antagonism of D-2 and 5-HT2 receptors and enhancement of DA and 5-HT release are critical elements in the action of clozapine to minimize both positive and negative symptoms without producing significant extrapyramidal symptoms or plasma PRL increases. It is proposed that schizophrenia may also involve a dysregulation of 5-HT2- and D-2-mediated neurotransmission, and that a more normal balance in serotonergic and dopaminergic neurotransmission is at least partially restored by clozapine.
 ...
PMID:Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. 268 29

Identification of 5-HT receptor subtypes--5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2 (possibly A and B), 5-HT3 subtypes, and possibly 5-HT4--has encouraged the manufacture of 5-HT receptor inhibitors with greater subtype specificity. However, it appears that the receptors interact, and drugs initially thought to be specific may have multiple actions. For some conditions such as anxiety/depression, almost all receptors are implicated. Clinical studies provide clear evidence that manipulation of the 5-HT system has a role in treating depression, anxiety, obsessional illness, migraine, and eating disorders. Interactions between the various receptor subtypes make it difficult to identify specific clinical functions. The 5-HT1A receptors may be involved in aggression, anorexia, and hypotension. The 5-HT1B receptors may be involved in aggression, while the 5-HT1C receptors may play a role in central aversion systems and anxiety/depression. The role of the 5-HT1D receptors remains speculative; 5-HT2 receptors appear to be involved in depression, anxiety, appetite, sleep, vasoconstriction, and hypertension. Many drugs that are effective in treating migraine are potent 5-HT2 antagonists. 5-HT3 antagonists at high doses are effective in treating nausea and at low doses in treating anxiety. Treatment of aggression, suicidal behaviour, addiction behaviour, memory impairment, dementia, and schizophrenia with 5-HT inhibitors requires further testing.
 ...
PMID:Is there a relationship between serotonin receptor subtypes and selectivity of response in specific psychiatric illnesses? 269 41

The platelet is one of the most researched biological markers in psychiatry. Characteristics of MAO activity, 5-HT uptake, imipramine and alpha 2-adrenergic receptor binding, for example, are similar in platelet and CNS. Methodological factors are not negligible, and range from diagnostic specificity and drug effects to the normal physiological variability of age and hormone-related changes, circadian and seasonal rhythms. As yet, there are no clear state or trait platelet markers in affective disorders and schizophrenia that can be unequivocally used to detect vulnerability to the illness, predict therapeutic response, define clinical diagnostic entities or follow the course of the illness. However, platelet markers are increasingly being used in careful studies to monitor psychopharmacological effects (an in vivo assay of all active metabolites), different ligands can be specific markers for certain aspects of a psychiatric illness (e.g. alpha 2-adrenergic receptors and weight loss), and this homogeneous preparation of human cells is an increasingly important tool in studying mechanisms in pathophysiology. More longitudinal studies are required to establish functional relationships between platelet variables and psychopathology.
 ...
PMID:Platelet research in psychiatry. 283 Oct 76

Fear is an adaptive response of the organism to external threat and the physiologic and behavioral responses to stimuli that induce fear involves activation of the sympathetic nervous system. Drugs that alter the function of two of the major brain monoamine neurotransmitter systems involved in sympathetic nervous system regulation (NE and 5-HT) have been shown to alter levels of "fear and anxiety" in laboratory animals, healthy humans, and patients. The relative clinical efficacy in the treatment of anxiety disorders with many of these drugs also emphasizes the importance of these two systems in anxiety. Recent advances in neuropharmacology have led to an improved understanding of how drugs that interact at specific NE and 5-HT receptors alter the function of these two neurotransmitter systems, and a few of the drugs that selectively interact at NE and 5-HT receptors have been used in studies of patients with anxiety disorders. Stimulation of the 5-HT system does not produce marked abnormalities in patients, but stimulation of the NE system does produce abnormal changes in measures of anxiety, somatic symptoms, blood pressure, and a plasma NE metabolite and cortisol levels in patients with panic disorder but not in patients with generalized anxiety disorder, obsessive-compulsive disorder, depression, or schizophrenia. This indicates that some patients with panic disorder have an abnormality in the regulation of the NE system that could explain many of the clinical features of this syndrome. Progress in assessing neurochemistry in the brains of living patients through brain imaging and new advances in the molecular biology of neurotransmitter receptor proteins will offer important new methods to be used in the study of these possible abnormalities.
 ...
PMID:Monoamine receptor systems and anxiety disorders. 284 38

Neuroleptic classifications try to take account of both biological effects (interaction with different neurotransmitters, selectivity of action on dopaminergic structures or dopaminergic subclasses of receptors) and clinical effects (sedative properties, efficacy on positive or negative symptomatology of schizophrenia, antimanic effect). Zotepine blocks mainly dopaminergic, 5-HT 2 and alpha 1 receptors. It should therefore be expected to have sedative properties in humans and to be effective against mania and the positive symptoms of schizophrenia.
 ...
PMID:Classification of neuroleptics--zotepine. 288 76

The concentration of platelet serotonin (5-HT) and the simultaneous uptake of 5-HT into platelets have been investigated in schizophrenic patients with (A) intermittent time course of illness (complete remission), (B) chronic time course (partial remission and residual symptoms), and (C) intermittent-chronic time course (good remission at the beginning of illness with gradual progression to chronic stage). An increased platelet 5-HT concentration (i.e., hyperserotoninemia) of unknown etiology was observed, especially in the group with chronic time course of disease as compared to the normal controls. At the same time, kinetic constants Km and Vmax of 5-HT uptake into platelets were unchanged in all patients. Neuroleptic treatment did not produce any significant change either in platelet 5-HT level or in the uptake of 5-HT. These results provide further support for the possible 5-HT dysfunction in schizophrenia.
 ...
PMID:Time course of schizophrenia and platelet 5-HT level. 289 41

Five vervet monkeys were administered increasing doses (4--12 mg/kg/day) of d-amphetamine over a period of 35 days. Three phases od behavioural change were discerned: phase 1 during which animals exhibited repetitive stereotyped action sequences with rapid head movements, occasional abnormal grooming, picking at the cage, hand-staring and snatching; phase 2 in which behaviour became progressively more restricted and animals became markedly unresponsive to auditory, visual and tactile stimuli; phase 3 was characterised by the abrupt development of gross over-responsiveness to environmental stimuli, ataxia and tremor. At post-mortem, by comparison with controls, amphetamine-treated monkeys showed marked depletions of the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in corpus striatum and cerebral cortex and reductions in the activities of tyrosine hydroxylase and dopa decarboxylase in striatum. Turnover of these monoamines, assessed by high-performance liquid chromatography determinations of their respective metabolites, was also reduced. These findings are interpreted as evidence of monoamine neurone destruction, most severely in the case of DA neurones. Though there was a non-significant reduction in 3H-spiperone binding (reaching almost 50% in nucleus accumbens), numbers of receptors for the monoamines nA and 5-HT were not significantly changed, and the activities of the enzymes choline acetyltransferase and glutamine decarboxylase were similar in experimental and control animals. The contrast of these findings with those seen in post-mortem brains in schizophrenia is discussed.
 ...
PMID:Behavioural and biochemical effects of chronic amphetamine treatment in the vervet monkey. 613 May 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>