Structure-activity relationships and drug allergy.
Structure-activity relationships (SARs) refer to the relation between chemical structure and pharmacologic activity for a series of compounds. Since the pioneering work of Crum-Brown and Fraser in 1868, they have been increasingly used in the pharmaceutical, chemical and cosmetic industries, especially for drug and chemical design purposes. Structure-activity relationships may be based on various techniques, ranging from considerations of similarity or diversity of molecules to mathematical relationships linking chemical structures to measured activities, the latter being referred to as quantitative SAR or QSAR. This review aims at briefly reviewing the history of SARs and highlighting their interest in delayed and immediate drug allergy using selected examples from the literature. Studies of SAR are commonly conducted in the area of contact dermatitis, a delayed hypersensitivity reaction, to determine the allergenic potential of a given compound without animal testing. In immediate, immunoglobulin E-mediated drug hypersensitivity, this kind of approach remains rather confidential. It has been mainly applied to neuromuscular blocking drugs (muscle relaxants) and betalactam antibiotics (penicillins, cephalosporins). This review shows that SARs can prove useful to (i) predict the allergenic potential of a chemical or a drug, (ii) help identify putative antigenic determinants for each patient or small group of patients sharing the same cross-reactivity pattern, and (iii) predict the likelihood of adverse reactions to related molecules and select safe alternatives.
Allergy Diseases: Diagnosis and Therapeutics, Department of Internal Medicine, Clinical Immunology and Allergology, University Hospital of Nancy, Nancy Cedex, France. f.hasdenteufel@orange.fr
Frederic
F
Hasdenteufel
Samuel
S
Luyasu
Nicolas
N
Hougardy
Malcolm
M
Fisher
Michel
M
Boisbrun
Paul-Michel
PM
Mertes
Gisele
G
Kanny
D000818:Animals; D003429:Cross Reactions / Q000276:immunology; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology; D015195:Drug Design; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000276:immunology; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D004364:Pharmaceutical Preparations / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship; D013997:Time Factors
D004364:Pharmaceutical Preparations; D007073:Immunoglobulin E