ABSTRACT
The present structure-activity relationship (SAR) study focused on chemical modifications of the structure of the local anesthetic lidocaine, and indicated analogues having reduced anesthetic potency, but with superior potency relative to the prototype in preventing anaphylactic or histamine-evoked ileum contraction. From the SAR analysis, 2-(diethylamino)-N-(trifluoromethyl-phenyl) and 2-(diethylamino)-N-(dimethyl-phenyl) acetamides were selected as the most promising compounds. New insights into the applicability of non-anesthetic lidocaine derivatives as templates in drug discovery for allergic syndromes are provided.
Subject(s)
Anesthetics, Local/chemical synthesis , Anesthetics, Local/pharmacology , Lidocaine/analogs & derivatives , Lidocaine/chemical synthesis , Lidocaine/pharmacology , Parasympatholytics/chemical synthesis , Parasympatholytics/pharmacology , Anesthetics, Local/chemistry , Animals , Combinatorial Chemistry Techniques , Dose-Response Relationship, Drug , Histamine/pharmacology , Lidocaine/chemistry , Molecular Structure , Parasympatholytics/chemistry , Rats , Structure-Activity RelationshipABSTRACT
It is presumed that drugs able to prevent bronchial spasm and/or inflammation may have therapeutic potential to control asthma symptoms. The local anaesthetic lidocaine has recently received increased attention as an alternative form of treatment for asthmatic patients. This paper reviews the major findings on the topic and summarizes the putative mechanisms underlying the airway effects of local anaesthetic agents. We think that lidocaine extends the spectrum of options in asthma therapy, probably by counteracting both spasmogenic and inflammatory stimuli in the bronchial airways. The possibility of development of new anti-asthma compounds based on the synthesis of lidocaine derivatives is also on the horizon.
Subject(s)
Anesthetics, Local/therapeutic use , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Lidocaine/therapeutic use , HumansABSTRACT
It is presumed that drugs able to prevent bronchial spasm and/or inflammation may have therapeutic potential to control asthma symptoms. The local anaesthetic lidocaine has recently received increased attention as an alternative form of treatment for asthmatic patients. This paper reviews the major findings on the topic and summarizes the putative mechanisms underlying the airway effects of local anaesthetic agents. We think that lidocaine extends the spectrum of options in asthma therapy, probably by counteracting both spasmogenic and inflammatory stimuli in the bronchial airways. The possibility of development of new anti-asthma compounds based on the synthesis of lidocaine derivatives is also on the horizon.
