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E J Ariëns

Publications and source records attributed to E J Ariëns.

At least 19 recordsLinked to original sources
PubMed1993

Nonchiral, homochiral and composite chiral drugs.

Chirality and the implicit stereoselectivity in pharmacodynamics and pharmacokinetics, in particular of racemic therapeutics, are interesting from both scientific and applied points of view. There is much literature on the subject, including a series of papers on chirality in TiPS in 1986 (Vol. 7, pp. 20-23, 60-64, 112-116, 155-158, 200-205 and 281-285). The choice between single stereoisomers (homochiral drugs) and composite chiral drugs (mixtures of stereoisomers) depends upon therapeutic advantages (such as a reduction in xenobiotic load), possible adverse side-effects and development costs. There is a need for critical evaluation of existing and new composite chiral drugs, while the potential of nonchiral drugs is hardly discussed in the literature. This review by E. J. Ariëns considers current information on composite, homo- and nonchiral drugs, with particular regard to drug development.

Animals↗
PubMed1991

Racemic therapeutics--ethical and regulatory aspects.

Racemic therapeutics are fixed ratio mixtures of stereoisomers to be regarded biologically as different compounds. Usually only one of the isomers fully contributes to the therapeutics action, and the other is often classifiable as "isomeric ballast". Due to differences in turnover and pharmacokinetics, the proportion of enantiomers (1:1 in the racemate) continuously changes in plasma. The implications of the neglect of stereoselectivity for various levels in the investigation of racemic drugs are discussed and summarized in Table 2. The fact is that clinical investigators, Ethical Committees and regulatory authorities have for decades accepted invalid pharmacokinetic data on some 25% of therapeutics. That those racemates remain in use make the benefit of and necessity for kinetics generally questionable. Exposure of patients to the "isomeric ballast" present in about 50% of the most commonly used drugs will probably contain for many decades. As a result of a change in attitude of the regulatory authorities, however, for new drugs the choice in future between the racemic therapeutic or the single isomeric ballast-free drug will largely be based on a critical evaluation of the chiral characteristics with regard to their therapeutic, toxicological and pharmacokinetic aspects.

Drug Therapy, Combination↗
PubMed1991

Receptors and dormant receptors--messengers and opportunistic ligands.

On the basis of the question what came first, the messenger or its specific receptor, the relation between the receptor concept and the messenger concept is discussed. Special attention is paid to opportunistic ligands that serve as messenger molecules and to dormant receptors, receptor-like proteins of unknown function. It is concluded that there is no receptor without a messenger and no messenger without a receptor.

Animals↗
PubMed1990

Stereoselectivity in pharmacodynamics and pharmacokinetics.

Stereoisomers of bioactive products, particularly drugs and pesticides, usually differ greatly in their biological properties. Usually only one of the enantiomers, the eutomer, is largely responsible for the therapeutic action. The distomer, the "isomeric ballast", must be considered an impurity which often contributes to, or is even the main cause of, the undesired actions of the racemate. A fundamental requirement is to "reduce the xenobiotic load" to the feasible minimum. This implies "avoiding isomeric ballast". The implications of the use of racemic products are largely ignored in scientific publications and in the marketing of drugs and pesticides. The problem is illustrated by the results of pharmacological investigations into the racemic drugs labetalol and medroxalol.

Adrenergic alpha-Antagonists↗
PubMed1984

Simultaneous assay of muscarinic and beta-adrenergic receptors using a double isotope technique.

Muscarinic receptor and beta-adrenergic receptor binding were measured simultaneously in a membrane fraction of bovine tracheal smooth muscle using [3H]-L-quinuclidinyl benzilate and [125I]-(-) iodocyanopindolol. The binding characteristics, affinity and receptor density, obtained in the double receptor assay and in the control experiments were the same within experimental error. Moreover, there appears to be neither a significant influence of an excess of d,1-propranolol on [3H]-L-quinuclidinyl benzilate binding nor a significant influence of an excess of 1-quinuclidinyl benzilate on [125I]-(-)iodocyanopindolol binding. The method is advantageous where both receptors have to be assayed and where limited amounts of biological material, like in biopsy specimen, are available.

Animals↗