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Dive into the research topics where Donald Stribling is active.

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Featured researches published by Donald Stribling.


British Journal of Pharmacology | 1991

ICI D7114 a novel selective β‐adrenoceptor agonist selectively stimulates brown fat and increases whole‐body oxygen consumption

Brian Roy Holloway; Ralph Howe; Balbir Singh Rao; Donald Stribling; Rachel M. Mayers; Martyn G. Briscoe; Jacqueline M. Jackson

1 ICI D7114 is a novel, β‐adrenoceptor agonist which stimulates whole body oxygen consumption in conscious rats, cats and dogs and brown adipose tissue (BAT) activity in conscious rats. Treatment of rats with ICI D7114 stimulated oxygen consumption (ED50, 0.04 mg kg−1, p.o.) and BAT mitochondrial guanosine diphosphate (GDP)‐binding (ED50, 0.15 mg kg−1, p.o.) with no chronotropic effects on the heart at these doses. 2 Reference β‐adrenoceptor agonists, isoprenaline and clenbuterol, also stimulated oxygen consumption and BAT activity but were less selective because they also produced effects on heart rate at these doses. 3 Treatment of conscious rats with ICI D7114 did not attenuate the chronotropic effects on the heart of a subsequent isoprenaline challenge. 4 Administration of ICI D7114 or of its acid metabolite had no effect in a cat soleus muscle model of tremor or on blood potassium levels in the conscious dog, indicating lack of effects at β2‐adrenoceptors. 5 The results indicate that ICI D7114 may have activity at atypical β‐adrenoceptors in brown adipose tissue leading to increased whole body oxygen consumption.


Journal of Medicinal Chemistry | 1992

Selective .beta.3-adrenergic agonists of brown adipose tissue and thermogenesis. 1. [4-[2-[(2-Hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetates

Ralph Howe; Balbir Singh Rao; Brian Roy Holloway; Donald Stribling

The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate (8) has been identified as the most interesting member of a series of selective beta 3-adrenergic agonists of brown adipose tissue and thermogenesis in the rat. In vivo it acts mainly via the related acid 10. Potency was generally markedly reduced by placing substituents on the phenyl ring of the phenoxypropanolamine unit of 8; only the 2-fluoro analogue 16 had comparable potency to 8. Other structure-activity relationships are discussed. Further testing of 8 (ICI 198157) has shown that in the rat it stimulates the beta 3-adrenergic receptor in brown adipose tissue at doses lower than those at which it affects beta 1 and beta 2 adrenergic receptors in other tissues. It increases metabolic rate, as judged by an increase in oxygen consumption, and in the genetically obese Zucker rat it causes a reduced rate of weight gain. This class of compound may be useful in the treatment of obesity in man.


The American Journal of Clinical Nutrition | 1992

ICI D7114: a novel selective adrenoceptor agonist of brown fat and thermogenesis.

Brian Roy Holloway; Ralph Howe; Balbir Singh Rao; Donald Stribling

Increasing energy expenditure by treatment with thermogenic drugs is not new, but available drugs have suffered from the problem of lack of selectivity. In the last decade two key findings have allowed the development of selective thermogenic drugs that have promise in the treatment of obesity. 1) The recognition that brown adipose tissue (BAT) plays a role in compensatory increases in energy expenditure has allowed an approach directed at a target organ. 2) The demonstration showing that increases in the activity of BAT may be modulated by an atypical (beta 3) adrenoceptor has led to the development of a new peripherally acting beta-adrenoceptor agonist ICI D7114, which stimulates thermogenesis at doses that have little effect on beta 1 or beta 2 adrenoceptors. Treatment with the compound activates BAT and thermogenesis even in species and situations where the intrinsic capacity is low. 3) The compound has beneficial effects in animal models of obesity and disturbed glucose and lipid homeostasis.


Biochemical Pharmacology | 1982

Endotoxin and tryptophan-induced hypoglycaemia in rats

Peter Lloyd; Donald Stribling; Christopher I. Pogson

Pretreatment of rats with increasing, but non-lethal, doses of endotoxin was associated with a parallel increase in sensitivity to induction of hypoglycaemia by tryptophan. Acutely streptozotocin-diabetic animals became hypoglycaemic with endotoxin alone, and this was increased further by tryptophan. Variations in tryptophan sensitivity between rat populations cannot be explained by previous history of exposure to endotoxin. Endotoxin abolished the increase in tryptophan dioxygenase activity caused by triamcinolone, but not that caused by tryptophan. Triamcinolone was effective, however, when given together with tryptophan to endotoxin-treated rats. The activity of tryptophan dioxygenase in vivo and in liver cells in vitro is unchanged by exposure to endotoxin at 1 mg/kg body wt. Turnover studies indicated that hypoglycaemia resulted from inhibition of gluconeogenesis. There was no evidence to support a role for insulin in this process and results were consistent with an endotoxin-mediated hepatic insensitivity to glucagon. They also suggested that quinolinate, rather than 5-hydroxytryptamine, may be the intracellular agent responsible for inhibition of gluconeogenesis.


Biochemical Pharmacology | 1982

Factors affecting tryptophan-induced hypoglycaemia in rats.

Peter Lloyd; Stephen A. Smith; Donald Stribling; Christopher I. Pogson

The mechanisms whereby tryptophan administration leads to hypoglycaemia in some groups of rats but not others have been investigated. Animals insensitive to tryptophan are rendered responsive by adrenalectomy. This effect is reversed by steroid replacement. Turnover studies with [2-3H]glucose show that hypoglycaemia in sensitive animals is associated with a decrease in glucose synthesis. Tryptophan administration causes a marked and sustained increase in plasma glucagon concentrations in all animals. The locus of the inhibition of gluconeogenesis in tryptophan-sensitive animals is the reaction catalysed by phosphoenolpyruvate carboxykinase. The sensitivities to tryptophan of gluconeogenesis in isolated hepatocytes from normal and adrenalectomized animals were similar. Cells from chronically streptozotocin-diabetic animals required higher concentrations of the amino acid for the same effect. These results are discussed in relation to previous discrepancies in the literature, and a unifying hypothesis for tryptophan-induced hypoglycaemia is proposed.


Biochemical Journal | 1986

Purified rat lens aldose reductase. Polyol production in vitro and its inhibition by aldose reductase inhibitors.

Peter F. Kador; Jin H. Kinoshita; D R Brittain; Donald J. Mirrlees; Christopher M. Sennitt; Donald Stribling


The Practitioner | 1987

Method of treatment of obesity

Brian Roy Holloway; Ralph Howe; Balbir Singh Rao; Donald Stribling


Archive | 1986

2-hydroxy-3-phenoxypropyl amines

Brian Roy Holloway; Ralph Howe; Balbir Singh Rao; Donald Stribling


Archive | 1991

Use of ethoxy phenoxy acetic acid derivatives against diabetes

Brian Roy Holloway; Donald Stribling


Biochemical Journal | 1987

Rat lens aldose reductase and polyol production: a reply

Peter F. Kador; Jin H. Kinoshita; Donald Stribling; David Robert Brittain; Donald J. Mirrlees; Christopher M. Sennitt

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Brian Roy Holloway

Imperial Chemical Industries

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Ralph Howe

Imperial Chemical Industries

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Balbir Singh Rao

Imperial Chemical Industries

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Donald J. Mirrlees

Imperial Chemical Industries

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Peter Lloyd

Imperial Chemical Industries

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Jin H. Kinoshita

National Institutes of Health

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Peter F. Kador

National Institutes of Health

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