Drugs relationships

Speciai risk Seizures, irrespective of drug relationship, occurred in 0.5% of patients during study therapy plus 14-day follow-up period. These experiences have occurred most commonly in patients with CNS disorders (eg, brain lesions or history of seizures) or compromised renal function. 

Holtzman, S.G., Discriminative stimulus effects of drug relationship to abuse liability, in Testing and Evaluation of Drugs of Abuse, M.W. Adler and A. Cowan, Eds., Wiley-Liss, New York, 1990. 

Clinical Use of Antibacterial Drugs Relationship to Specific Bacterial Infections... 

Chang, J.T., Altman, R.B. 2004. Extracting and characterizing gene-drug relationships from the literature. Pharmacogenetics. 14(9) 577-586. 

Chemistry produces many materials, other than drugs, that have to be optimized in their properties and preparation. Chemoinformatics methods will be used more and more for the elucidation and modeling of the relationships between chemical structure, or chemical composition, and many physical and chemical properties, be they nonlinear optical properties, adhesive power, conversion of light into electrical energy, detergent properties, hair-coloring suitabHty, or whatever. 

Kubinyi H 1995. The Quantitative Analysis of Structure-Activity Relationships. In Wolff M E (Editor) Burger s Medicinal Chemistry and Drug Discovery. 5th Edition, Volume 1. New York, John Wiley Sons, pp. 497-571. 

When the property being described is a physical property, such as the boiling point, this is referred to as a quantitative structure-property relationship (QSPR). When the property being described is a type of biological activity, such as drug activity, this is referred to as a quantitative structure-activity relationship (QSAR). Our discussion will first address QSPR. All the points covered in the QSPR section are also applicable to QSAR, which is discussed next. 

In the case of drug design, it may be desirable to use parabolic functions in place of linear functions. The descriptor for an ideal drug candidate often has an optimum value. Drug activity will decrease when the value is either larger or smaller than optimum. This functional form is described by a parabola, not a linear relationship. 

Thus, a drug may produce response either with low efficacy by occupying many receptors or with high efficacy by occupying few receptors. The issues of dealing with agonist—dose response relationships can be complex and reference should be made to detailed texts (44,45). 

II. RELATIONSHIPS BETWEEN EXPERIMENTAL AND THEORETICAL APPROACHES TO STUDYING DRUG-RECEPTOR INTERACTIONS... 

GR Marshall, CD Barry, HE Bosshard, RA Dammkoehler, DA Dunn. The conformational parameter m drug design The active analog approach. ACS Symp Ser 112 205-226, 1979. JL Fauchere, ed. QSAR Quantitative Structure-Activity Relationships m Drug Design. New York Alan R Liss, 1989, pp 177-181. 

It has long been known that quaternary ammonium salts can exert a curare-like action, and in recent years much attention has been given to the synthesis and pharmacological testing of such products work on this subject up to 1936 has been reviewed by Ing, and more recently a theoretical discussion of the relationship between structure and action in drugs of this type has been provided by Holmes, Jenden and Taylor.Chase, Lehmann and Yonkmann have compared the action of quaternary salts of quinine with that of -erythroidine hydrochloride and of dihydro- -erythroidine hydrobromide. Quinine ethochloride shows marked curariform action of short duration. ... 

Among others, 11 was included in a series of drugs to study quantitative structure-activity relationships (96KFZ(6)29, 98MI7, 99BMC2437). A statistically significant CoMFA model was developed for describing the... 

A chance observation made some time prior to the full structural elucidation of cocaine in fact led to one of the more important lasses of local anesthetics. It was found that the simple ethyl e. ter of p-aminobenzoic acid, benzocaine (25), showed activity. 1-. a local anesthetic. It is of interest to note that this drug, I 1rst introduced in 1903, is still in use today. Once the struc-iiire of cocaine was established, the presence of an alkanolamine iiiniety in cocaine prompted medicinal chemists to prepare esters "I aminobenzoic acids with acyclic alkanolamines. Formula 26 11 presents the putative relationship of the target substances with cocaine. 

The isosteric relationship of benzene and thiophene has often led medicinal chemists to substitute the sulfur containing heterocycle for benzene drugs in biologically active molecules. That this relationship has some foundation in fact is attested by the observation that the resulting analogs often possess full biologic activity. Alkylation of the diamine, 71 (obtained from aniline and the chloroethylamine), with 2-chloromethylthiophene affords the antihistamine methaphenylene (72) The correspond-... 

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