Publications by authors named "Sayers A"

Muscle samples from beef Longissimus dorsi (LD) were conditioned inv vacuo at 10°C for up to 21 days and then stored in a glycerol-extracted state at -20°C to determine how their mechanical properties were altered by the conditioning process. Muscle fibres were progressively more difficult to dissect as conditioning proceeded, but those dissected showed isometric mechanical tension in the presence of Ca(2+), relaxation in the absence of Ca(2+) and calcium sensitivity which did not vary with conditioning up to 8 days. Myofibrils prepared from the same conditioned tissue showed slight changes with conditioning time, namely an initial rise in Ca(2+)-activated ATPase followed by a later fall, a slow rise in ATPase in the absence of Ca(2+) and an increase in Ca(2+)-sensitivity.

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In 1101 goats and 547 sheep kept under ranch conditions the liveweight development was measured and compared between their 10th and 550th day of life. Consideration was given to factors such as sex, parity, birth type, season of birth, and flock. Post-partum weights of the dams are given and analysed for the same variables.

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5-Chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole (DS 103-282) is a centrally acting agent with a novel chemical structure and a pharmacological profile different from that of myotonolytic drugs in current use such as diazepam, baclofen and dantrolene. It inhibits alpha- and gamma-rigidity in rats, reflex muscle tone in rabbits and the linguomandibular reflex in cats at low doses, but has little or no effect on gross spinal reflexes or electrically-induced segmental reflexes in cats. The mechanism underlying the muscle relaxation is unknown.

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After repeated administration of classical neuroloptics to the rat, supersensitivity of striatal dopamine (DA) receptors towards DA-receptor agonists can be demonstrated. This effect can be quantified (a) by measuring the turning response to apomorphine in rats with unilateral striatal lesions or (b) by measuring the changes induced by neuroleptics in the DA metabolism in the striatum of intact rats. In these test systems, thioridazine induces an increase in DA-receptor sensitivity which is significantly less intense and of shorter duration than that induced by haloperidol.

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The tremorogenic properties of a series of benzylimidoylurea derivatives are described. The most potent member, N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON-954), produces a reproducible, dose-dependent rest tremor in the mouse with oral doses of 5-100 mg/kg which is also seen in other species (rat, cat, dog, rabbit). The tremor is of constant frequency, rapid onset and short duration.

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Structure-activity relationships of 16 dibenzoepines, including clozapine, loxapine, clothiapine and perlapine, have been investigated with regard to locomotor inhibition, cataleptogenesis, apomorphine antagonism, arousal inhibition, effect on striatal dopamine metabolism, and in vivo and in vitro anticholinergic potency. Thioridazine and the classical neuroleptics haloperidol and chlorpromazine were included in the study for comparison. The classical tests used to detect neuroleptic activity in laboratory animals were found to be poor predictors of possible clinical effectiveness of the dibenzo-epines.

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The effects of haloperidol, alone and in combination with atropine, were compared with the effects of clozapine, alone and in combination with physostigmine, in a variety of tests commonly used to characterize neuroleptic compounds. It was found that clozapine in combination with physostigmine did not present the profile of activity of a classical neuroleptic agent; neither did haloperidol in combination with atropine present that of clozapine. In fact, some effects of haloperidol (catalepsy) were antagonized by atropine, while others (induction of striatal DA-receptor hypersensitivity) were enhanced.

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The increase in the concentration of homovanillic acid (HVA) in the haloperidol for 6 days compared to a single administration of the drug. The induction of tolerance is probably due to a functional modification of the striatal dopamine (DA)-receptors after repeated administration of the neuroleptic. Atropine given in combination with haloperidol enhances the induction of tolerance.

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Tardive dyskinesias, often seen in patients treated with classical neuroleptics, have been attributed to the development of receptor hypersensitivity following prolonged blockade of dopamine (DA)-receptors. In rats with unilateral striatal lesions, development of DA-receptor hypersensitivity following a 6-day treatment with haloperidol can be demonstrated by means of the increased turning response to apomorphine. Addition of atropine to the haloperidol treatment schedule resulted in a further increase in receptor sensitivity, but with a delay of 24 h in its appearance.

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The effects of the peripheral and central alpha-adrenoceptor stimulant and antihypertensive agents clonidine and BS 100-141 (N-amidino-2[2,6-dichlorophenyl]acetamide - HCl) on EEG sleep patterns in rats and on blood pressure in pithed rats have been investigated. Whereas both compounds abolished paradoxical sleep (PS), clonidine, in contrast to BS 100-141, markedly increased the sleeping time. Both drugs caused a dose-dependent increase in the blood pressure of pithed rats.

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This paper discusses some of the pharmacological and neurochemical properties of clozapine, and the special attributes that differentiate clozapine from the classical neuroleptics. The question as to whether or not clozapine blocks DA-receptors--a crucial point in regard to the dopamine hypothesis of schizophrenia--has received particular attention. Neurochemical, neuropharmacological, and endocrinological evidence is presented which speaks against a DA-receptor blockade by clozapine in pharmacologically relevant doses.

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According to Venables the span of psychotic processes extends from a low level of arousal with an increased reactivity toward sensory stimuli to a high level of arousal with a reduced reactivity toward sensory stimuli. The level of arousal and the degree of reactivity, or breadth of attention, are apparently controlled by a regulatory mechanism which increases the threshold for sensory input in threatening situations. Any factor producing an electroencephalographic arousal reaction leads to a narrowing of attention.

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The present study has compared the abilities of clozapine, haloperidol, chlorpromazine and loxapine to induce dopamine (DA)-receptor hypersensitivity in rats, as measured by the apomorphine response after withdrawal of the antipsychotic drugs. Haloperidose during 1-2 weeks after withdrawal. Clozapine, given prior to apomorphine, reduced the responses of the haloperidol and loxapine groups to the control level.

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The purpose of this study is to assess the nature and magnitude of the deleterious health effects of subclinical over-exposure to lead in children. The study stems from concerns about the impact on the health of children in city slums who ingest leaded paint without overt evidence of poisoning and the health implication of rising levels of lead in the environment from automotive emissions. The study sample was derived mainly from a registry of children on whom blood lead determinations had been made by the New York City Department of Health and was supplemented by siblings of the registry cases and children from a lead belt area who had extractions of deciduous teeth in dental clinics.

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A single dose of alpha-methyl-p-tyrosine induced catalepsy in rats, commencing 6 h after administration. This catalepsy was strongly enhanced by (+)-amphetamine and (-)-ephedrine, but was antagonized by other amphetamine-like drugs. The implication of these findings is briefly discussed.

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