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Advances in Drug Research
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ISSN (Print) 0065-2490
Published by Elsevier

[3044 journals]

Prefa Farewell
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 30
  
  PubDate: 2012-12-17T15:55:41Z
The concept of emergence—dissolvence in drug research
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 30
  
  In this chapter, the creation of some complex systems of relevance to drug research, and the emergence of their specific properties, has been viewed from an unexplored perspective. Specifically, the chapter examines the property space of the components as they come together and enter coupling and synergy to create a complex system. The number of formal and functional states of the components decreases during this creation. This phenomenon is called dissolvence, and it can be recognized in the formation of complex systems at all levels of size and complexity. Dissolvence must not be viewed as destruction or loss but rather as a creative process, generating the information that allows the nascent system to appear and evolve to higher states of organization and emergence. Thus, the concept of dissolvence should be recognized as the inseparable counterpart of emergence. Both the emergence and the dissolvence of properties can help understand how complex systems are formed, behave, and evolve.
  
  PubDate: 2012-12-17T15:55:41Z
Sense and non-sense in toxicity assessment of medicinal products
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 30
  
  Toxicology is the science of chemically induced harmful effects to humans, the domestic animals or plants of humans, or the web of nature at large. Toxicology is a subdiscipline of natural science and should ideally not beget nonsense. Toxicology has developed like other life sciences along positivist lines and with an increasing speed. Especially in the last half of this century, toxicology grew in response to the requirements of industrial hygiene and industrial production of synthetic raw materials and pharmaca. Therefore, toxicology started sharing responsibility for the social implications (industrial medicine, public health) of the expansion of chemical industry and the use of its products.
  
  PubDate: 2012-12-17T15:55:41Z
The concept of chiral conformers and its significance in molecular
pharmacology
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 30
  
  Traditional chemistry is the science of configuration. Conformations present special problems owing to their flexibility and multiplicity; it is in the biological effect of molecules that the role of conformations becomes highly important. Drug research appears to have an interest in highly skilled techniques, such as combinatorial chemistry, and high throughput screening instead of trying to find conceptual advances. The work of robots may prove reliable like that of a lawnmower without overlooking a piece of straw. Biological environment does not accept flexible molecules as rigid structures. On the contrary, the binding site distorts the molecule; much like a hungry mouth chews on a bite of food. Chirality of conformers, therefore, represents the problem; how they can be modified. Hence, it is not only a static shape that can be chiral, but the distortion of the conformer may be brought about in mirror image alternatives.
  
  PubDate: 2012-12-17T15:55:41Z
Combinatorial compound libraries for enhanced drug discovery approaches
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 30
  
  This chapter focuses on combinatorial compound libraries for enhanced drug discovery approaches. The chapter describes the basic principles of combinatorial technologies such as arrays, combinatorial chemistry with split synthesis, expression libraries, highly diverse libraries, thematic libraries, analog series, and library formats. The chapter also covers the issues related to planning, design, and theoretical interpretation and illustrates how to manage screening and synthesis data, handling combinatorial structure information, searching through combinatorial data, statistical aspects of mixture libraries, assessing diversity, comparing combinatorial libraries, designing libraries, and evolutionary synthesis. The chapter also discusses the chemical libraries such as oligomer libraries, small-molecule libraries, and tagging, encoded libraries.
  
  PubDate: 2012-12-17T15:55:41Z
Reversal of chloroquine resistance in malaria: A new concept of
chemotherapy
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 30
  
  Despite the fact that the finer details of the mechanism of chloroquine (CQ) action and the cause of resistance in plasmodia are still being researched, the development of a resistance reversal agent has become a distinct possibility. The major impediment for the in vivo evaluation against the chloroquine resistant plasmodium falciparum is the non-availability of aotus monkey. Several reports on CQ resistance reversal by a number of drugs in combination with CQ suggest that the therapeutic use of any combination may be recommended only after the pharmacokinetic and toxicological studies. This becomes mandatory because the drug–drug interactions that are bound to take place may change the pharmacokinetic and toxicological profile of the individual components.
  
  PubDate: 2012-12-17T15:55:41Z
Cumulative index of authors
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 30
  
  PubDate: 2012-12-17T15:55:41Z
Cumulative index of titles
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 30
  
  PubDate: 2012-12-17T15:55:41Z
Peptidomimetics in drug design
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 29
  
  The number of peptidic drugs is constantly increasing, and this trend will continue in the future. Many of the compounds are currently under clinical investigation, whereas others were introduced for human therapeutic use. The gonadotropin-releasing hormone and somatostatin-release inhibiting factor analogs belong to the last category. Despite the disadvantages referred in this chapter, the development of peptide-based receptor ligands will certainly remain of interest in the future. The marked trend in recent years is the design and development of orally active non-peptide ligands for peptide receptors. Of significance in this regard is the fact that it is possible to imitate or block the pharmacological effect of a relatively large peptide at the receptor level with low molecular mass compounds. The opioid alkaloids are excellent examples for this fact.
  
  PubDate: 2012-12-17T15:55:41Z
Medicinal photochemistry: Phototoxic and phototherapeutic aspects of drugs
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 29
  
  The variety in molecular structure of phototoxic drugs is immense. This implies that almost all classes of compounds contain members with adverse photobiological effects. Careful in vitro and in vivo investigations can help estimate the risk that phototoxicity will show to be a side-effect. This kind of research is all the more needed before commercialization, because photoreactivity of drugs in the body can be the cause of side-effects of both topical and systemic nature. Medicinal photochemistry can provide the knowledge of the part of the molecular structure that is responsible for the phototoxicity of a particular drug. With this insight, analogs can be found that still have the desired pharmacological activity but are deprived of phototoxicity.
  
  PubDate: 2012-12-17T15:55:41Z
Development of estrogen antagonists as pharmaceutical agents
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 29
  
  Estrogenicity lowering agents are gaining increasing importance in various pharmaceutical areas. Their use is indicated where the presence of estrogens is the cause of the ailment or their selective biological manifestation is needed. Compounds may be developed that inhibit estrogen synthesis. However, because estrogen is involved in many ways with normal human physiology, inhibition of estrogen synthesis may lead to complications, and its use may be restricted to extreme diseases such as cancer. Estrogen antagonists, or competitive inhibitors of estrogens, generally have both agonistic and antagonistic properties. The ratio of the two activities is crucial for their different requirements as pharmaceuticals. Based on ligand–receptor interaction studies, structural requirements for estrogen agonist activity have been worked out. Compounds resembling estradiol with appropriately positioned receptor-binding parameters can be designed to have potent estrogenic activity.
  
  PubDate: 2012-12-17T15:55:41Z
Peroxidic antimalarials
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 29
  
  Peroxidic antimalarials are well established as a new drug class. However, the possibility of the development of resistance by the malarial parasite should not be ignored. Synergistic effects with conventional nitrogen-containing antimalarials or drugs, such as atovaquone, which by themselves are therapeutically inadequate, are worth exploring. It also seems likely that chloroquine, because of its diminishing efficacy for treating malaria, will be gradually replaced, not by another quinolinebased antimalarial or even a first-generation derivative of artemisinin, but by a simple peroxidic antimalarial.
  
  PubDate: 2012-12-17T15:55:41Z
Cumulative index of authors
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 29
  
  PubDate: 2012-12-17T15:55:41Z
Cumulative index of titles
- Abstract: 1997
  Publication year: 1997
  Source:Advances in Drug Research, Volume 29
  
  PubDate: 2012-12-17T15:55:41Z
Prefa Circles in drug research
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 28
  
  PubDate: 2012-12-17T15:55:41Z
Stereochemical aspects of drug action and disposition
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 28
  
  This chapter provides background information on the implications of stereochemistry for drug action and disposition. It focuses on the principles involved and uses illustrative examples to demonstrate the implications for the therapeutic use of chiral drugs. For racemic drugs in widespread use data on stereoselectivity in action, disposition and toxicity should be available. Once this information is known, each drug is evaluated on a case-by-case basis to determine whether a single enantiomer may offer a therapeutic advantage to the racemate. Although one cannot expect practicing physicians to know of all the details associated with the stereochemistry of the racemic drugs they prescribe, they should be aware of the phenomena. The chapter discusses the development of drug. Although only a limited number of the many racemic drugs in therapeutic use have been investigated with regard to stereoselectivity of action and disposition, the results clearly demonstrate that it is not valid to consider these drugs as single compounds. In view of the differences in activity and disposition that can exist between enantiomers, two drugs have been administered when a racemic medicine is prescribed and two cases have been considered in assessing the merits and benefits of employing enantiomerically pure drugs.
  
  PubDate: 2012-12-17T15:55:41Z
Advances in the development of pharmaceutical antioxidants
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 28
  
  This chapter attempts to narrow the gap where antioxidant pharmacology meets with organic chemistry. It is intended to serve as a reference to substances that have been described, designed, or developed as therapeutically relevant antioxidants. It is obvious that the present contribution cannot cover more than a limited number of examples of antioxidants from the large variety of structural classes that have been studied as possible drug candidates. For this purpose, it most fruitful to cover compounds that have emerged from in vitro experimentation and structure–activity studies. The chapter discusses antioxidant effects in molecular and structural terms. The synthetic compounds have been classified chemically, rather than by therapeutic area, as the latter, in most instances, is a matter of the preference of the researchers rather than inherent properties of the substances. Some ranges regarding dose or concentration have been included to indicate the approximate potencies of compounds, especially when standard in vitro assays have been utilized. The enzyme systems that are devoted to detoxification of reactive and potentially pathological oxygen metabolites have also been thoroughly treated by others, and will be mentioned to provide a basis for the discussion of synthetic enzyme mimics. The chapter attempts to present the various conceivable approaches that are at hand for attenuating oxidative tissue injury and the harmful effects that are ascribed to free radicals.
  
  PubDate: 2012-12-17T15:55:41Z
Multidrug resistance of cancer cells
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 28
  
  This chapter focuses primarily on recent reports relating to issues that remain unresolved in the field of multidrug-resistance and on developments that have come to the forefront in the past few years. After a brief overview of mdr genes and P-glycoprotein, (Pgp) activity, it discusses the clinical relevance of the human MDR1 gene and Pgp, the mechanism by which Pgp confers drug-resistance and the regulation of MDR1 gene activity in normal and cancer cells. The chapter briefly reviews what is known about other cellular mechanisms for conferring resistance to mdr-related drugs and the clinical aspect of mdr by discussing prospects for overcoming multidrug-resistance in light of what is now known about its mechanisms of action. MDR1 or mdr has been used generically to refer to mammalian genes functional in conferring multidrug-resistance.
  
  PubDate: 2012-12-17T15:55:41Z
Bioactivation of organic nitrates and other nitrovasodilators
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 28
  
  This chapter discusses nitric oxide and cyclic guanosine monophosphate as mediators of organic nitrate action and formation of nitric oxide from organic nitrates in cell-free systems. Organic nitrates have been classified as prodrugs releasing the pharmacologically active metabolite nitric oxide. Although several different pathways have been suggested, recent evidence points to a cytochrome P450 system playing an important role in the process of enzymatic nitric oxide generation from organic nitrates. The chapter attempts to answer some unanswered questions such as, “Is cytochrome P450 relevant for the action of organic nitrates in vivo'” and “Is cytochrome P450 involved in nitrate tolerance'” Although there is considerable evidence that cytochrome P450 mediates nitric oxide formation from organic nitrates in vitro, the relevance of this pathway in vivo has still to be determined. It is possible to restore nitric oxide production and inhibit intimal hyperplasia in endothelium-denuded rat carotid arteries by in vivo transfer of the endothelial cell nitric oxide synthase gene. This finding suggests nitric oxide synthase to be a potential target for gene therapy in disease states such as atherosclerosis or restenosis following balloon angioplasty.
  
  PubDate: 2012-12-17T15:55:41Z
The vitamin D endocrine system and its therapeutic potential
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 28
  
  This chapter is devoted to describing the vitamin D endocrine system, how the active hormonal form of vitamin D works, and the potential for treatment of a variety of diseases, ranging from metabolic bone diseases to such diverse disorders as psoriasis and cancer. With the discovery of the activation of the vitamin D molecule has come the application of the metabolites of vitamin D and its analogues to human disease. The discovery of the vitamin D receptor in tissues has resulted in the discovery of new functions of vitamin D, as its involvement in the differentiation and development of the monocyte from the promyelocyte. A further detailed analysis of the role of 1,25-Dihydroxyvitamin D3 in initiating transcription of target genes will yield new information that will be of value not only in understanding these complex systems but in providing guidance to maximize treatment of disease.
  
  PubDate: 2012-12-17T15:55:41Z
Dopamine receptors: Studies on structure and function
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 28
  
  This chapter considers the information that has emerged recently on dopamine receptors from the application of the techniques of molecular biology to the dopamine receptors. It considers the mechanism of ligand binding to dopamine receptors from a theoretical and experimental standpoint. It should be clear throughout that the knowledge gained with molecular biological techniques has revolutionized the ability to study and conceptualize dopamine receptors. The application of biochemical, pharmacological, and physiological techniques to the study of dopamine receptors showed that there are multiple receptors for dopamine, and it was proposed that there were two subtypes of dopamine receptor (D1 and D2). These had distinct biochemical and pharmacological properties and a summary of the properties of these two subtypes has been given. Hydrophobic interactions with aromatic residues provide an important contribution to the free energy of binding. The contributions of these interactions to the overall free energy of the ligand binding process have been estimated and the experimental observations reported are consistent with the need for several favorable interactions between ligand and receptor to compensate for the unfavorable process of ligand binding and to lead to receptor activation.
  
  PubDate: 2012-12-17T15:55:41Z
Cumulative index of authors
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 28
  
  PubDate: 2012-12-17T15:55:41Z
Cumulative index of titles
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 28
  
  PubDate: 2012-12-17T15:55:41Z
Foreword
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  PubDate: 2012-12-17T15:55:41Z
Abbreviations
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  PubDate: 2012-12-17T15:55:41Z
Introduction
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  PubDate: 2012-12-17T15:55:41Z
Regulation of glucose homoeostasis
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  The glucose regulatory system is one of the most important homoeostatic systems in physiology. Glucose homoeostasis is the sum of various processes that regulate the production and metabolism of glucose in vivo. In healthy individuals, fuel homoeostasis and blood glucose levels are remarkably well maintained. The fundamental mechanism underlying the regulation of glucose homoeostasis is complex. The maintenance of glucose homoeostasis depends on substrate supply, primarily glucose ingestion and glucose uptake (peripheral and splanchnic), insulin secretion, hormonal counter-regulation, and hepatic glucose efflux (gluconeogenesis and glycogenolysis). These processes are simultaneously ongoing and are coordinated physiologically to avoid hypo- and hyper-glycaemic states. In the postabsorptive state, normal blood glucose levels are maintained by hepatic glucose production from gluconeogenesis and glycolysis. Extrahepatic tissues utilize glucose, and corresponding amounts of glucose are provided by the liver, thus keeping glucose homoeostasis in balance. It is found that insulin physiologically released in a pulsatile fashion is the key regulatory factor of glucose homoeostasis. Conversely, the major regulator of insulin secretion is plasma glucose concentration. Insulin suppresses glucose output of the liver and stimulates glucose uptake by extrahepatic peripheral tissues, primarily muscle, and adipose tissue.
  
  PubDate: 2012-12-17T15:55:41Z
Clinical aspects of diabetes mellitus
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  This chapter discusses the aetiology, clinical symptoms and prognosis of Type-I and II diabetes mellitus. The type I is the result of an immunologically mediated genetically programmed destruction of the B-cells. In type II diabetes there is a relative deficit in insulin-secretory capacity. It is documented that by several humoral and cellular immunological abnormalities precedes the clinical onset of the disease type I and the development of Type-II diabetes requires a genetic component which predisposes to the disease, an abnormality in pancreatic B-cell function and the presence of insulin resistance in skeletal muscle, adipose tissue and the liver. The onset of the autoimmune disease Type-I diabetes has a protracted prodromal period. Overt symptoms such as hyperglycaemia occur only months and years after initial metabolic and immunological abnormalities such as impaired glucose tolerance, ICA and IAA are noted. The classic symptoms of metabolic disturbance are rare in Type-II diabetes and more insidious than in Type-I. Hyperglycaemia, thirst, polyuria, and fatigue are the classic symptoms, but weight loss is infrequent and diagnosis is often made after intercurrent infections or as an incidental finding.
  
  PubDate: 2012-12-17T15:55:41Z
Mechanisms of insulin action
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  Insulin action is initiated by binding of the hormone to its specific receptor at the plasma membrane. This induces a broad spectrum of distinct effects at a number of different target cells, predominantly in muscle, liver, and fat. These cellular insulin effects can be divided into four categories: stimulation of membrane transport processes (ions, glucose, amino acids); anabolic effects including the stimulation of glycogen synthesis, lipogenesis and protein synthesis; anticatabolic effects such as the inhibition of lipolysis, proteolysis, and glycogenolysis; growth-promoting effects in certain cell types, i.e. stimulation of RNA and DNA synthesis in concert with other anabolic effects. Insulin action involves rapid events (seconds to minutes) such as the stimulation of ion and glucose transport, stimulation of phospholipid turnover, generation of mediators and enzyme regulation including glycogen synthase, pyruvate dehydrogenase, triacylglycerol lipase and phosphorylase among others. Insulin also stimulates slow events (minutes to hours) such as the activation of amino acid transport, protein, and lipid synthesis or stimulation of RNA and DNA synthesis. It is believed that all these different effects are initiated by binding of insulin to a single type of receptor, whereas a branching of signal transduction occurs at a post-binding or even post-receptor level.
  
  PubDate: 2012-12-17T15:55:41Z
Therapeutic use of insulin
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  Insulin is used for the treatment of Type-I and for Type-II diabetes mellitus, when other therapeutic measures, i.e. appropriate diet and oral antidiabetics are not sufficient to produce normoglycaemia. Since treatment of diabetes with insulin attempts only to supplement inadequate insulin secretion, this chapter concentrates on pharmacokinetics, unwanted effects, and clinical applications of insulin and its pharmaceutical preparations. Pharmacokinetical parameters of exogenously administered insulin resemble those of physiological insulin, it differs from physiological secretion of insulin in at least two major ways: the kinetics of absorption of subcutaneously or intramuscularly administered insulins are relatively slow and thus do not mimic the normal rapid increase and decline in insulin secretion in response to ingestion of nutrients; the insulin diffuses into the peripheral circulation instead of being released into the portal circulation. This may account for the differences in the action between physiological secretion and therapeutic administration of insulin. Extreme caution is necessary in the measurement of dosage; inadvertent overdose may lead to an irreversible insulin shock. Serious consequences may result if insulin is not used under constant medical supervision.
  
  PubDate: 2012-12-17T15:55:41Z
The secretory machinery of insulin release
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  Type-II diabetes is characterized by relatively deficient insulin secretion in response to glucose, peripheral insulin resistance, and increased hepatic glucose production. Among oral antidiabetic drugs, sulphonylureas will be active and enhance insulin release. To understand the mechanism of the action of these drugs, this chapter summarizes the present knowledge about the physiology of the so-called stimulus-secretion coupling. Moreover, this chapter also provides the physiological basis for possible future development of antidiabetic drugs which may promote discharge of insulin in a way that is different from that of sulphonylureas. Secretion of insulin results from the action of initiators and modulators on the secretory mechanism. Whereas initiators cause the discharge of insulin by depolarization of the B-cell and subsequent influx of Ca 2+, modulation (i.e. amplification and/or attenuation) is mediated mainly by activating and/orinactivating the adenylate cyclase and/or phospholipase C systems. Studies exploring the mechanism of insulin secretion face a number of technical and physiological problems which must be considered when scientific data on this subject are interpreted. Thus, islet tissue is only available in small amounts, its composition is not homogeneous and its reaction to initiating/modulating compounds may differ among species and even between islets when localized in different areas of the pancreas. Enriched islet-derived single B-cells, on the other hand, do not react in the same way as do complete pancreatic islets intact islets of Langerhans, clonal insulinoma cells grown in culture are used to study the physiology of the secretory mechanism.
  
  PubDate: 2012-12-17T15:55:41Z
Compounds acting on insulin secretion: Sulphonylureas
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  The hypoglycaemic activity of sulphonylureas was detected by chance as a side effect of certain sulphonamides used for the treatment of typhoid fever. These observations led to clinical trials that promoted the development of sulphonylureas as oral hypoglycaemic agents. Two actions are thought to be responsible for their ability to lower glucose concentration in blood: their action on B-cells which causes insulin secretion; the so-called extrapancreatic effects which have been mainly demonstrated in in vitro experiments. Two generations of sulphonylureas have been developed which differ in chemical structure and potency. The most prominent difference between first- and second-generation sulphonylureas is the higher affinity of specific binding of the latter which in turn causes much higher stimulation of insulin secretion and therefore significantly decreases the doses needed.
  
  PubDate: 2012-12-17T15:55:41Z
Compounds acting on glucose uptake: Biguanides
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  This chapter discusses the chemistry, pharmacology, pharmacokinetics, toxic effects, interactions with other drugs, and clinical studies of biguanides, a compounds acting on glucose uptake. Metformin and phenformin are biguanides. The mode of action of metformin is complex and not fully understood. It decreases blood glucose levels of diabetics and adipose non-diabetics, but not of normal subjects. It does not stimulate insulin release but does require that some insulin be present for it to exert a hypoglycaemic effect. Interpretation of the changes in insulin binding after metformin dosing is still controversial. Although metformin may increase insulin receptor binding, its main effect appears to be directed at the post-receptor level of insulin action. Acute poisoning with metformin calls for intensive supportive therapy. Lactacidosis may require treatment with sodium bicarbonate or furosemide, a combination of insulin and glucose or peritoneal dialysis or haemodialysis. It is observed that biguanides do not affect glycaemia in normal individuals and do not increase insulin output. However, because the liver is the dominant site of action in a physiological in vivo situation, hepatic glucose transport is reduced leading to increased hepatic insulin sensitivity.
  
  PubDate: 2012-12-17T15:55:41Z
Compounds acting on glucose absorption
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  This chapter discusses the chemistry, actions, pharmacokinetics, toxicity, interaction with other drugs, and clinical studies of compounds acting on glucose absorption such as Guar, Acarbose. Guar is derived from the endosperm of the seed Cyamopsis psoraloides and it postpones the absorption of carbohydrates. Acarbose is a pseudotetrasaccharide in which one maltose is exchanged for a pseudomaltose. Guar gum is used in diabetes mellitus as an adjunct to treatment with diet, insulin or oral hypoglycaemics because it is considered to reduce the peak blood glucose concentrations that occur following meals. Acarbose decreases alimentary hyperglycaemia and is therefore used in diabetes. The efficacy of guar is dependent mainly on its capacity to hydrate rapidly and thus to increase viscosity in the small intestine postprandially. Measurement of the rate of hydration in vitro might be a useful index of the effectiveness of guar formulations. Acarbose competitively inhibits α-glucosidases that are important for the degradation of disaccharides during digestion. They are specific for α-connected glucose and digest non-absorbable di-, oligo- and poly-saccharides to absorbable monosaccharides.
  
  PubDate: 2012-12-17T15:55:41Z
Aldose reductase inhibitors as new antidiabetic drugs
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  The participation of aldose reductase in the development of diabetic complications is assumed to be based on a triad of tissue effects: sorbitol accumulation, myo-inositol depletion and decreased activity of Na/K- ATPase. Most aldose reductase inhibitors (e.g. sorbinil, alrestatin, tolrestat, and ponalrestat) inhibit the enzyme in a non-competitive or uncompetitive way—they compete neither with the substrate nor with the cofactor (NADPH). The development of aldose reductase inhibitors as useful drugs is actually at the stage of evaluation of their pharmacodynamic benefit. Data on the pharmacokinetic properties of these drugs are therefore rather scarce. In addition, owing to their chemical heterogeneity, no common principles can be established. It is found that renal dysfunction reduces the clearance of tolrestat, with corresponding increases in the half-life. No effect was reported on the volume of distribution or absorption, suggesting that the dose should be reduced in renal failure. The fact that one-third of the dose is eliminated by the liver makes it possible to use the drug even in both liver and kidney dysfunction if the possible doubling in the plasma levels is compensated by a reduction in the dosage. Unsuccessful development is often due to toxicological problems which remain unpublished. Hence little is publicly known about the toxicity of aldose reductase inhibitors.
  
  PubDate: 2012-12-17T15:55:41Z
Conclusions
- Abstract: 1996
  Publication year: 1996
  Source:Advances in Drug Research, Volume 27
  
  PubDate: 2012-12-17T15:55:41Z