Effects of the D-1 agonist SKF-38393 combined with haloperidol in schizophrenic patients.
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2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Biomedical subjects
K L Davis
Publications and source records attributed to K L Davis.
Increased morbid risk for schizophrenia-related disorders in relatives of schizotypal personality disordered patients.
To evaluate whether probands from a clinical sample diagnosed as having DSM-III schizotypal and/or paranoid personality disorder have a familial relationship to the schizophrenia-related disorders, the morbid risk for schizophrenia-related disorders and other psychiatric disorders were evaluated in the first-degree relatives of patients with schizotypal and/or paranoid personality disorder and compared with the corresponding risk for these disorders in the first-degree relatives of patients with other non-schizophrenia-related personality disorders. The morbid risk for all schizophrenia-related disorders, and specifically for schizophrenia-related personality disorders, was significantly greater among the relatives of the probands with schizotypal and/or paranoid personality disorder than among the relatives of probands with other personality disorder. The morbid risk for other psychiatric disorders did not differ significantly between the first-degree relatives of the schizotypal/paranoid personality disorder and the other personality disorder control proband samples. These results suggest a specific familial association between schizophrenia-related disorders, particularly schizophrenia-related personality disorders, and clinically diagnosed schizotypal patients.
Adolescent↗
Attentional markers of vulnerability to schizophrenia: performance of medicated and unmedicated patients and normals.
Medicated and unmedicated schizophrenic patients (both n's = 14) were compared to a normal control sample (n = 15) on two attentional tasks hypothesized to be markers of vulnerability to schizophrenia. These tasks, the continuous performance test and the visual backward masking task, were found to be more deviant in schizophrenic patients than in normals. In addition, the group mean levels of performance did not differ consistently across medication status within the medicated patients. It was found, however, that the association between these tasks varied as a function of medication status, with unmedicated patients more similar to normals than to medicated patients. The implications of these results for the two tasks as markers are discussed, with special focus on those earlier studies that did not evaluate unmedicated patients.
Attention↗
Implications of multiple transmitter system lesions for cholinomimetic therapy in Alzheimer's disease.
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Acetylcholinesterase↗
Hormonal stimulation of 12(R)-HETE, a cytochrome P450 arachidonic acid metabolite in the rabbit cornea.
12(R)-HETE [12(R)-hydroxy-5, 8, 10, 14 eicosatetraenoic acid] is one of the major arachidonic acid metabolites produced by microsomal cytochrome P450 of the corneal epithelium. This metabolite is a potent inhibitor of Na(+)-K(+)-ATPase activity in several tissues. We investigated endogenous production of 12(R)-HETE in the rabbit corneal epithelium. Incubation of corneal epithelial sheets (prelabeled with 14C-arachidonic acid) with arginine vasopressin resulted in the production of radioactive 12(R)-HETE suggesting its formation from endogenously labeled-arachidonic acid. The maximal response was obtained with 1 microM arginine vasopressin and represents a 15-fold increase in 12(R)-HETE formation compared with that of control tissues. Stimulation of 14C-arachidonic acid release with a detergent, digitonin, also resulted in endogenous 12(R)-HETE formation. Analysis of the incubation media following digitonin treatment of prelabeled corneal epithelial sheets revealed that 12(R)-HETE production was maximal at 20 microM digitonin, a 17-fold increase over control values. This study is the first to describe hormonal and traumatic stimulation of 12(R)-HETE formation from endogenously labeled arachidonic acid in intact corneal tissues. This study demonstrates that the formation of this Na(+)-K(+)-ATPase inhibitor can be modulated by physiological and pathophysiological regulation.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Therapeutic trials using tacrine and other cholinesterase inhibitors.
At this time, the data available on tacrine are inconclusive with respect to efficacy. Preliminary data are often overinterpreted, and it seems prudent to wait for the results of the ongoing multicenter double-blind studies before reaching a definite conclusion about efficacy.
Alzheimer Disease↗
Interactions of forebrain cholinergic and somatostatinergic systems in the rat.
The neurochemical, behavioral and pharmacological effects of forebrain cholinergic and somatostatinergic deficits were assessed in adult rats. Brain somatostatinergic activity was manipulated by the systemic administration of different doses of cysteamine. Forebrain cholinergic systems were lesioned by the infusion of ibotenic acid into the nucleus basalis of Meynert (nbM). Forebrain cholinergic lesions did not affect forebrain somatostatin-like-immunoreactivity (SLI). Depletion of forebrain SLI by cysteamine did not significantly affect forebrain cholinergic marker activity. The combination of forebrain cholinergic deficits with forebrain somatostatinergic deficits did not lead to any greater impairment of mnemonic function than that produced by lesions alone, nor did SLI deficits hamper the efficacy of physostigmine to enhance memory in sham operated or nbM-lesioned rats. These results suggest that although forebrain cholinergic and somatostatinergic systems do interact at some levels, this interaction is a minor one with respect to neurochemical, behavioral or pharmacological variables.
Animals↗
Attenuation of nucleus basalis of Meynert lesion-induced cholinergic deficits by nerve growth factor.
Nerve growth factor (NGF) was administered into either the lateral ventricle or into the basal forebrain of n. basalis of Meynert (nbM) lesioned rats. Rats received either continuous infusion of 5 micrograms of 7S NGF per day for 28 days, or 5 micrograms of 7S NGF on 4 occasions distributed evenly during the first two post-lesion weeks. The administration of NGF reduced lesion-induced cortical cholinergic marker deficits by approximately 50%, irrespective of the locus or mode of NGF administration. Thus NGF is able to attenuate lesion-induced cholinergic deficits across a range of treatment and lesion conditions.
Animals↗
Cyclic-AMP production by polymorphonuclear leukocytes in psychiatric disorders.
The cyclic adenosine monophosphate (cAMP) responses to histamine, prostaglandin-E1, and isoproterenol in polymorphonuclear leukocytes from drug-free normal controls and patients with schizophrenia or major depressive disorder were compared. These three groups of subjects did not differ in their cAMP responses to receptor activation. Exacerbated and remitted patients with either schizophrenia or major depressive disorder did not differ in their cAMP responses. The data indicate that in polymorphonuclear leukocytes, the cAMP responses to activation of histamine H2, prostaglandin-E1, or beta-adrenergic receptors are neither state-independent nor state-dependent markers for schizophrenia or major depressive disorder.
Adult↗
Serotonergic studies in patients with affective and personality disorders. Correlates with suicidal and impulsive aggressive behavior.
Dysfunction of the central serotonergic system has been variously associated with depression and with suicidal and/or impulsive aggressive behavior. To evaluate central serotonergic function in relation to these variables, prolactin responses to a single-dose challenge with fenfluramine hydrochloride (60 mg orally), a serotonin releasing/uptake-inhibiting agent, were examined in 45 male patients with clearly defined major affective (n = 25) and/or personality disorder (n = 20) and in 18 normal male control patients. Prolactin responses to fenfluramine among all patients were reduced compared with responses of controls. Reduced prolactin responses to fenfluramine were correlated with history of suicide attempt in all patients but with clinician and self-reported ratings of impulsive aggression in patients with personality disorder only; there was no correlation with depression. These results suggest that reduced central serotonergic function is present in a subgroup of patients with major affective and/or personality disorder and is associated with history of suicide attempt in patients with either disorder, but with impulsive aggression in patients with personality disorder only.
Adult↗
Regional differences in the induction of behavioral supersensitivity by prolonged treatment with atypical neuroleptics.
Some atypical neuroleptics have been shown to exert selective effects on the nigrostriatal or mesolimbic dopamine systems as assessed by behavioral, biochemical and electrophysiological measures. This specificity appears to occur using chronic or acute schedules of drug administration. This study examined the effect of chronic administration of haloperidol, clozapine, sulpiride and metoclopramide on stereotypy and locomotor activity elicited by direct injection of dopamine in to the striatum or nucleus accumbens, respectively. Each rat was pre-treated with a neuroleptic drug or vehicle control for 21 days. Five days after the termination of drug treatment, each rat was injected with 10 micrograms dopamine bilaterally, and stereotypy or locomotor activity was measured. Rats pre-treated with metoclopramide exhibited an enhanced stereotypy response, and rats pre-treated with haloperidol, clozapine or sulpiride exhibited enhanced locomotor activity compared to controls. The extent to which these results demonstrate the selective action of these drugs in sensitizing dopamine systems is discussed.
Animals↗
Eye tracking, schizophrenic symptoms, and schizotypal personality disorder.
Schizophrenic patients and patients with schizotypal personality disorder were significantly more likely than normal controls to demonstrate impaired eye tracking performance. Fifteen of 27 schizophrenics and 15 of 27 schizotypals had impaired eye tracking, compared with 11 of 39 normal controls. In the schizophrenic group, including 10 out-patients in a stable state of relative remission, impaired eye tracking was associated with more severe formal thought disorder and more time spent in psychiatric hospitals. Among stable schizophrenic out-patients, poor eye tracking was related to more severe formal thought disorder and greater overall psychopathology. This pattern of results suggests a possible relation between eye tracking impairment and more severe enduring symptoms across the spectrum of schizophrenic and schizophrenia-related disorders.
Adult↗
9-Amino-1,2,3,4-tetrahydroacridin-1-ols: synthesis and evaluation as potential Alzheimer's disease therapeutics.
The synthesis of a series of 9-amino-1,2,3,4-tetrahydroacridin-1-ols is reported. These compounds are related to 1,2,3,4-tetrahydro-9-acridinamine (THA, tacrine). They inhibit acetylcholinesterase in vitro and are active in a model that may be predictive of activity in Alzheimer's disease--the scopolamine-induced impairment of 24-h memory of a passive dark-avoidance paradigm in mice. Two compounds, (+/-)-9-amino-1,2,3,4-tetrahydroacridin-1-ol maleate (1a, HP-029) and (+/-)-9-(benzylamino)-1,2,3,4-tetrahydroacridin-1-ol maleate (1p, HP-128), were also active in reversing the deficit in 72-h retention of a one-trial dark-avoidance task in rats, induced by ibotenic acid lesions in the nucleus basalis magnocellularis. In addition, compound 1 p showed potent in vitro inhibition of the uptake of radiolabeled noradrenaline and dopamine (IC50 = 0.070 and 0.30 microM, respectively). Compounds 1a and 1p, which showed less acute toxicity in both rats and mice than THA, are in phase II and phase I clinical trials, respectively, for Alzheimer's disease.
Alzheimer Disease↗
Corrections to a 1980 article on CSF monoamine metabolites.
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3,4-Dihydroxyphenylacetic Acid↗
Dementia with coexistent major depression.
Eleven percent (N = 25) of 232 dementia patients seen in an active geropsychiatry service also met criteria for major depression. Ten patients with dementia/depression were prospectively compared with 10 non-depressed demented and 33 nondemented depressed patients on pretreatment and posttreatment ratings of depression and cognition/memory. Seventy percent (N = 7) of the dementia/depression group and 73% (N = 24) of the depression-only group responded to antidepressant therapy. Signs and symptoms of depression complicating dementia were similar to depressive phenomena in the depression-only group. Depression with dementia appeared to lower performance on cognitive tests. Following treatment, although cognitive impairment remained in the demented range, test performance improved.
Aged↗
Premorbid sociosexual functioning and long-term outcome in schizophrenia.
Chronic schizophrenic patients with the most severe social deterioration have been shown to differ from other chronic schizophrenic patients with respect to measures of left-to-right ventricular asymmetry, negative symptoms, and response to haloperidol treatment. In the current study, the authors investigated the social antecedents of these characteristics of very poor outcome schizophrenia in 69 chronic schizophrenic patients. Poor premorbid sociosexual functioning was associated with more severe left-to-right ventricular asymmetry, greater severity of negative symptoms, fewer positive symptoms, and worse current social functioning. These data suggest that factors associated with severe social deterioration in the end stage of schizophrenia are also associated with premorbid sociosexual impairment.
Adult↗
A study of the reliability of the family history method in genetic studies of Alzheimer disease.
The reliability between 2 raters conducting independent family history interviews for Alzheimer disease-like and other dementias was investigated. The interviews were conducted at least 1 year apart with the second rater blind to the data collected by the first rater. Raters agreed on the presence and type of dementia in 153 relatives age 45 or older of 30 AD probands, the age at onset in secondary cases, and the age of nonaffected relatives.
Aged↗
Combined administration of physostigmine and clonidine to patients with dementia of the Alzheimer type: a pilot safety study.
Reports of cholinergic and noradrenergic deficits in brain specimens from Alzheimer patients have suggested that concomitant augmentation of cholinergic and noradrenergic neurotransmission can benefit some dementia of the Alzheimer type (DAT) patients. However, pharmacological agents that enhance central cholinergic and noradrenergic neurotransmission, like physostigmine and clonidine, might have serious adverse effects. Therefore, prior to the commitment of major resources in efficacy studies, feasibility pilot studies are necessary to ensure that physostigmine and clonidine, combined, can be safely administered to DAT patients. Physostigmine, 2 mg every 2 h, and clonidine, up to 0.3 mg/day, were tolerated by the nine DAT patients without clinically meaningful adverse effects.
Aged↗