title: Metabolic stability of new anticonvulsants in body fluids and organ homogenates.
abstract: The stability as a function of time of compounds with established anticonvulsant activity: picolinic acid benzylamide (Pic-BZA), picolinic acid 2-fluorobenzylamide (Pic-2-F-BZA), picolinic acid 3-fluorobenzylamide (Pic-3-F-BZA), picolinic acid 4-fluorobenzylamide (Pic-4-F-BZA) and picolinic acid 2-methylbenzylamide (Pic-2-Me-BZA) in body fluids and homogenates of body organs were determined after incubation. It was found that they decompose relatively rapidly in liver and kidney and are stable against enzymes present in body fluids and some organs. These results are consistent with the bond strength expressed as total energy of amide bonds (calculated by quantum chemical methods) in the studied anticonvulsants. The calculated values of the amide bond energy are: 199.4 kcal/mol, 200.2 kcal/mol, 207.5 kcal/mol, 208.4 kcal/mol and 198.2 kcal/mol, respectively. The strength of the amide bonds in the studied anticonvulsants correctly reflects their stability in liver or kidney.
authors.affiliation: Department of Drug Chemistry, Medical University of Warsaw, 1 Banacha St., 02-097 Warszawa, Poland. dorota.marszalek@wum.edu.pl
authors.forename: Dorota
authors.initials: D
authors.lastname: Marszałek
authors.forename: Anna
authors.initials: A
authors.lastname: Goldnik
authors.forename: Franciszek
authors.initials: F
authors.lastname: Pluciński
authors.forename: Aleksander P
authors.initials: AP
authors.lastname: Mazurek
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubiak
authors.forename: Ewa
authors.initials: E
authors.lastname: Lis
authors.forename: Piotr
authors.initials: P
authors.lastname: Tazbir
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Koziorowska
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism*; D002474:Cell-Free System; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D010848:Picolinic Acids / Q000737:chemistry / Q000378:metabolism*; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000927:Anticonvulsants; D010848:Picolinic Acids; C030614:picolinic acid