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)

It has been suggested that sigma receptor antagonists may be useful as antipsychotic drugs and that 5-hydroxytryptamine (5-HT2) receptor antagonists produce improvements of the negative symptoms of schizophrenia. [1-(Cyclopropylmethyl)-4-(2'-(4''-fluorophenyl)-2'- oxoethyl)-piperidine HBr] (DuP 734) is a novel compound with high affinity for the sigma (Ki = 10 nM) and 5-HT2 (Ki = 15 nM) receptors, but low affinity for dopamine receptors (Ki > 1000 nM) as well as 33 other receptors, ion channels and second messenger systems in vitro. DuP 734 did not inhibit the synaptosomal uptake of dopamine, 5-HT or norepinephrine. Oral administration of DuP 734 potently blocked 5-hydroxy-L-trytophan (5-HTP)-induced head twitch in the rat (ED50 = 6.5 mumol/kg), indicating 5-HT2 antagonist activity. Extracellular single-unit recording studies demonstrated that DuP 734 antagonized the effect of the selective sigma ligand (+)-3-(3-hydroxyphenyl-N-(1-propyl) piperidine [(+)-3-PPP] on dopamine neuronal activity in the substantia nigra of the rat with an ED90 of 3.6 mumol/kg i.v. The sigma receptor agonists (+)-SKF 10,047 and phencyclidine both elicited rotational behavior in rats with unilateral lesion of the substantia nigra. The rotational behavior induced by either (+)-SKF 10,047 or phencyclidine was dose-dependently antagonized by DuP 734 with oral ED50 of 8.7 and 19.6 mumol/kg, respectively. The 5-HT2 receptor antagonist ICI 169,369, even at high doses (up to 33 mumol/kg, s.c.), did not antagonize the rotational behavior induced by (+)-SKF 10,047.(ABSTRACT TRUNCATED AT 250 WORDS)
J Pharmacol Exp Ther 1992 Dec
PMID:DuP 734 [1-(cyclopropylmethyl)-4-(2'(4''-fluorophenyl)-2'-oxoethyl)- piperidine HBr], a sigma and 5-hydroxytryptamine2 receptor antagonist: receptor-binding, electrophysiological and neuropharmacological profiles. 136 72

In this study a symptom self-regulation model was used as a framework to examine the characteristics and stability of indicators of illness identified by individuals with schizophrenia. Subjects were interviewed to determine if they could identify indicators of illness and describe characteristics of their primary indicator. Primary indicators of illness from 51 subjects were categorized as anxiety-based, depressive, or psychotic. Subjects who identified psychotic indicators were more confident that their indicator occurred when they were getting ill than subjects with anxiety-based or depressive indicators, and subjects who identified psychotic and depressive indicators reported that their indicators were more troublesome than those identifying anxiety-based indicators. Anxiety-based indicators were reported by subjects to occur more frequently than indicators from the other two categories. Findings from a follow-up interview of 28 subjects 1 year later showed that approximately half reported either the same primary indicator of illness or identified an indicator in the same category (anxiety-based, depressive, or psychotic) as they had 1 year previously. The implications of the findings for enhancing self-care through monitoring symptoms are discussed.
Arch Psychiatr Nurs 1992 Dec
PMID:Symptom monitoring in schizophrenia: potential for enhancing self-care. 136 50

Dose-effect studies have found that 600 mg/day of chlorpromazine (or its equivalent) is generally sufficient to treat acute psychosis. This paper reports on the doses of antipsychotic medication prescribed for inpatients in a Schizophrenia Unit at an Australian state hospital. Fifty five percent of patients received daily doses equivalent to more than 600 mg of chlorpromazine and 26% received daily doses equivalent to more than 1500 mg of chlorpromazine. Low potency drugs were prescribed in lower doses than high potency drugs. Patients prescribed depot medication tended to receive higher doses of medication than those prescribed oral medication only.
Aust N Z J Psychiatry 1992 Dec
PMID:Antipsychotic drug doses in a schizophrenia inpatient unit. 136 51

This report describes a patient with schizophrenia who developed episodes of ocular dystonia as a delayed side effect of neuroleptic medication. Each episode was preceded and accompanied by marked agitation, stereotypic behaviour and exacerbation of hallucinations. Both the psychotic and dystonic symptoms responded to anticholinergic medication. The theoretical and practical implications of this observation are discussed.
Aust N Z J Psychiatry 1992 Dec
PMID:Psychotic symptoms preceding ocular deviation in a patient with tardive oculogyric crises. 136 53

Dopamine (DA) D2, D3, and D4 receptors are targets for antipsychotic drugs. The recent cloning, deoxyribonucleic acid sequencing, and brain location of these receptors provide new insight on the DA hypothesis of schizophrenia, particularly for the basis of antipsychotic therapy of schizophrenia. In schizophrenia brain tissue, D2 receptors are elevated and have lost the link to D1 receptors. Brain positron-emission tomography studies of patients may also reveal elevated D2, depending on the method used. Hallucinations and positive symptoms are blocked when about 70% of the D2 receptors are occupied by neuroleptic drugs. An analysis of the literature indicates that therapeutic concentrations of antipsychotic drugs (in the patient's cerebrospinal fluid or plasma water) act primarily at D2 receptors, with the exception of clozapine, which acts at D4 receptors.
Neuropsychopharmacology 1992 Dec
PMID:Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4. 136 57

Human fetal brain tissue was obtained from first-trimester elective abortions of two women who also had schizophrenia. Portions of the embryonic hippocampus or cerebral cortex were transplanted into the anterior eye chamber of immunologically compromised athymic nude rats. In this environment, embryonic brain tissue derived from normal women generally continues organotypic growth and development for many months. Although initial survival after transplantation was normal, the tissue derived from schizophrenic women manifested less robust growth. However, cells in the transplants showed typical neuronal differentiation, with development of different neuronal types, such as pyramidal cells, granule cells, and gamma-aminobutyric acid (GABA)-containing interneurons. Rhythmic electrical activity was also observed, indicative of some local synaptic organization. The presence of messenger RNA (mRNA) for brain-derived neuronotrophic factor (BDNF) was observed using in situ hybridization. The reason for the decreased rate of growth of these transplants remains unknown and the significance of the finding cannot be assessed from only two fetuses. However, these preliminary findings suggest that fetal transplants may be a useful model system for the detection of developmental pathogenic processes in the expression and transmission of schizophrenia.
Biol Psychiatry 1992 Dec 15
PMID:Initial studies of embryonic transplants of human hippocampus and cerebral cortex derived from schizophrenic women. 136 85

Disturbances in dopamine neurotransmission have been postulated to underlie schizophrenia. We report data from two independent studies of a BalI polymorphism in the dopamine D3 receptor gene in patients with schizophrenia. In both studies, more patients than controls were homozygous (p = 0.005, p = 0.008). When pooled data were analysed, this difference was highly significant (p = 0.0001) with a relative risk of schizophrenia in homozygotes of 2.61 (95% confidence intervals 1.60-4.26).
J Med Genet 1992 Dec
PMID:Association between schizophrenia and homozygosity at the dopamine D3 receptor gene. 841 Oct 64

5-HT3 receptors have an exclusive neuronal location and evidence is presented of their involvement in behaviour. 5-HT3 receptor antagonists such as ondansetron, tropisetron and zacopride have provided the critical pharmacological tools to reveal a potent and efficacious ability to regulate disturbed behaviour. Thus the 5-HT3 receptor antagonists will restore to normal rodent and primate behaviour disturbed by increasing limbic dopamine function, aversive situations, cognitive impairments and drug abuse. The remarkable feature of their action is a failure to modify normal behaviour. This unique pharmacological signature has ensured a wide interest in the potential role of the 5-HT3 receptor antagonists in the treatment of schizophrenia, anxiety, age related memory impairment and the problems of withdrawal from drugs of abuse. The preclinical data and preliminary clinical observations are presented.
Pharmacol Toxicol 1992 Dec
PMID:Astra Award Lecture. The psychopharmacology of 5-HT3 receptors. 136 67

Iron status and akathisia were assessed in 105 long-stay in-patients who fulfilled DSM-III-R criteria for schizophrenia, all but three of whom were receiving antipsychotic medication. Chronic akathisia was diagnosed in 23% and pseudoakathisia in 20%. No significant correlation was found between serum iron concentration and the severity of akathisia. There was no significant difference in serum iron concentration between patients with chronic akathisia and those without. However, serum iron and percentage saturation were significantly raised in patients with pseudoakathisia compared with patients with chronic akathisia, and tended to be higher than in patients with akathisia. These findings do not support an association between low serum iron and chronic akathisia.
Br J Psychiatry 1992 Dec
PMID:Relationship between iron status and chronic akathisia in an in-patient population with chronic schizophrenia. 136 69

Sherrington et al. (1988) reported linkage between markers located on the 5q11-q13 region of chromosome 5 and schizophrenia in five Icelandic and two British families. To date, however, all attempts to replicate the initial finding have failed. Using three markers of chromosome 5, we have studied 28 additional French pedigrees. When our data were analyzed both with parametric (i.e., lod scores) and nonparametric methods, we found no evidence of linkage. Thus, we were unable to replicate the earlier report by Sherrington et al.
Psychiatry Res 1992 Dec
PMID:Failure to replicate linkage between chromosome 5q11-q13 markers and schizophrenia in 28 families. 136 50


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