A synopsis on different homologous series of fomocaine derivatives. In vitro interactions with the cytochrome P450 system, toxicity, and local anaesthetic effects in rats--Part 1.
Fomocaine (CAS 56583-43-6) is a basic ether-type local anaesthetic used in dermatological practice for surface anaesthesia. For many years, modifications of the fomocaine molecule have been pursued, e.g. to improve its physicochemical properties and also in view of possible new (systemic) applications, e.g. in the treatment of migraine or as antiarrhythmic. The present paper provides a survey of the investigations undertaken with all the different series of fomocaine derivatives synthesized so far with respect to their in vitro interaction capacity at the cytochrome P450 system, in vivo toxicity (LD50; paresis of the N. ischiadicus) and local anaesthetic effects (conduction anaesthesia at the N. ischiadicus; surface anaesthesia of the cornea) in rats. The main objective of this systematic comparison of the effects of all these substances was to assess possible basic structure-activity relationships.
Lupp
Amelie
A
Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, Germany. Amelie.Lupp@mti.uni-jena.de
Karge
Elke
E
Dahse
Thomas
T
Glassl
Peter
P
Jung
Beate
B
Listing
Monika
M
Seeling
Andreas
A
Wange
Johannes
J
Wennek-Klose
Janett
J
Oelschläger
Herbert
H
Fleck
Christian
C
D000779:Anesthetics, Local / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003315:Cornea / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D005260:Female; D007928:Lethal Dose 50; D049449:Luminescence; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009431:Neural Conduction / Q000187:drug effects; D009504:Neutrophils / Q000502:physiology; D010243:Paralysis / Q000139:chemically induced; D010647:Phenyl Ethers / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013748:Tetracaine / Q000494:pharmacology
D000779:Anesthetics, Local; D010647:Phenyl Ethers; D013748:Tetracaine; C100275:fomocain; D011343:Procaine; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1