Strategies For Antioxidant Therapy

In the broadest possible definition, an antioxidant is any chemical that attenuates the rate of oxidative degradation of the material or substrate under study. Halliwell and Gutteridge (1989) defined an antioxidant as any substance that, when present at low concentrations compared to those of an oxidizable substrate, significantly delays or inhibits oxidation of that substrate. However, when considering pharmaceutical relevant antioxidants, one may also need to include compounds that do not...

Alkaloids

The benzylisoquinoline tetrandrine (465), isolated from hanfangji, the root of Stephania tetrandra, which is used in traditional Chinese medicine, has been found to have beneficial effects in the treatment of silicosis (Seow et al., 1988). Tetrandrine has a suppressing effect on random movement, chemotaxis and phagocytosis of human neutrophils at a concentration of 10 xgmr1, but it inhibits superoxide generation from neutrophils at a considerably lower dose of 0.1 xg ml '. This effect was...

Phenolic Natural Products

Most natural products with antioxidant activity isolated from plants, e.g. curcumin, catechin, vitamin E, myricetin, quercetin, kaemferol, vanillin, gallic acid and caffeic acid, contain phenolic groups. Usually, at least two oxygen functions are present per aromatic moiety to provide sufficient stabilization of the formed phenoxyl radical. L liger (1991) has provided a short review of potential soures of natural antioxidants. However, many investigations used crude extracts rather than...

List Of Abbreviations

BHA Butylated hydroxyanisole, i.e. 2-ieri-butyl-4-methoxyphenol BHT Butylated hydroxy toluene, i.e. 2,6-di-teri-butyl-4-methylphenol CIBD Chronic inflammatory bowel disease DMPO 5,5-Dimethyl-l-pyrroline V-oxide radical EDRF Endothelium-derived relaxing factor EDTA Ethylenediamine tetra-acetic acid NSAID Non-steroidal anti-inflammatory agent PMNL Polymorphonuclear leukocytes PUFA Polyunsaturated fatty acid SARD Slow-acting antirheumatic drug TBARS Thiobarbituric acid-reactive substance TNBS...

Enantiomers Have The Same Activity But Differ In Potency

It has been proposed that the use of individual verapamil enantiomers instead of the racemate might offer certain advantages in special clinical settings (Powell et al., 1988). (S)-verapamil is only 1.5-2 times more potent than ( )-verapamil in increasing coronary blood flow and decreasing coronary resistance. However, with regard to negative chronotropic, dromotropic and inotropic, as well as its blood-pressure-lowering, effects much greater differences in potency have been noted (Table 1)....

Contents

Contributors vii Preface Circles in drug research viii Stereochemical Aspects of Drug Action and Disposition MICHEL EICHELBAUM AND ANNETTE S. GROSS 1 Introduction 2 Stereoselectivity in Drug Action 3 3 Stereoselectivity in Drug 4 Stereoselectivity and 5 Implications and 6 Drug Advances in the Development of Pharmaceutical Antioxidants CARL-MAGNUS ANDERSSON, ANDERS HALLBERG AND THOMAS HOGBERG 1 Introduction 2 Endogenous Defence 3 Semisynthetic Analogues of Endogenous Antioxidants 85 4 Natural 5...

Stereoisomers Are Equipotent

In various experiments, including (a) animal models of arrhythmias, (b) the binding affinity to receptors associated with cardiac sodium channels and (c) Fig. 2. In vitro activity of the enantiomers of mefloquine ((+), A ( ), A) and halofantrine ((+), o (-) ) against the chloroquine-resistant strain FCM29 of Plasmodium falciparum. Each point represents the mean of three to five replicate tests. No difference in the activity of the enantiomers is observed in this in vitro model. (Adapted from...

Antihyperlipoproteinaemic And Antihypertensive Drugs

Probucol (636), used clinically to lower blood cholesterol levels, is a powerful antioxidant, as expected from the structural similarities to phenolic antioxidants. Probucol has been shown to inhibit oxidative modification of LDL (Parthasarathy et al., 1986 McLean and Hagaman, 1989) and to prevent the secondary modification of the lysine groups on the surface of the LDL particle. In vitro evidence has been provided that the concentration of probucol in LDL determines the extent of oxidative...

Info

A-tocopherol in both in vitro assays. Kuno et al. (1992) have disclosed yet another series of cerebroprotective antioxidants containing piperazine and pyrimidine moieties. A series of 17 3-aminooxazolyl steroids (578) has been reported to possess local anti-inflammatory effects, which were attributed to an antioxidant capacity of the compounds (Rapi et al., 1985). It was shown by the authors that the 2-aminooxazole moiety needed to be attached to a steroid nucleus in order to show this...

Drug Development

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 are in fact being administered when a racemic medicine is prescribed. Should we, therefore, continue to administer racemic medicines or use...