Pharmacological profile of RWJ 20085: A new, potent, long‐acting local anesthetic

Abstract

(2.5 x 1 OP3M) and lidocaine (5.0 x I Op3M) produced a 50% reduction of the amplitude of the pretreatment action potential; however, bupivacaine and etidocaine were each effective at a lower concentration (5.0 x 1 O-4M). When their intramuscular therapeutic ratios (TR = lethal dose LD,,/l ocal anesthetic ED, , ) were calculated in mice, the therapeutic ratio of RWJ 20085 (82) was less than that of etidocaine (103) but was larger than that of either lidocaine (36) or bupivacaine (29). Calculation of the therapeutic ratios by using the intravenous LD, , values suggests that lidocaine would have the smallest margin of safety if inadvertently administered by the intravenous route. The therapeutic ratios of the other agents were larger than that of lidocaine; however, there was little difference among them. RWJ 20085 has a low potential for dermal irritation as shown in rabbits and has no liability for contact sensitization as shown in guinea pigs. RWJ 20085 may have clinical utility as an injectable and/or topical local anesthetic.

Aplysamine-1 and related analogs as histamine H3 receptor antagonists

“…2). [18][19][20] Recognizing the similarities between the natural product and the HTS hit, we chose to explore the structure-activity relationship (SAR) of aplysamine-1-based H 3 ligands. Herein the synthesis and biological activities of aplysamine-1 (1) and related analogs are reported.…”

Use of Ionic Liquids as Neoteric Solvents in the Synthesis of Fused Heterocycles

“…Imidazo[2,1‐ a ]isoquinolines are of interest due to their anti‐inflammatory potential , antirhinoviral , long‐acting local anesthetic properties , and as antiulcer agents . Hou et al used ionic liquid for the synthesis of imidazo[2,1‐ a ]isoquinolines 19 by stirring a mixture of α‐tosyloxyacetophenone 17 , 1‐aminoisoquinoline 18 , and Na 2 CO 3 in BPyBF 4 (Scheme ).…”

Iodobenzene‐Catalyzed Synthesis of Imidazo[1,2‐a]pyridines from Aryl Ketones with mCPBA in Ionic Liquid

“…Imidazo [1,2-a]pyridines are of interest due to their antiinflammatory, 1 potential antirhinoviral, 2 long-acting local anesthetic 3 and antiulcer agents, 4 for whitening fine fabrics, 5 as anthelmintic or bacteriostatic agents, 6 and as fluorescent materials. 7 They are also versatile intermediates for synthetic transformations.…”