Interaction of benzocaine with model membranes.
We measured the absorption properties, water solubility and partition coefficients (P) between n-octanol, egg phosphatidylcholine (EPC) liposomes and erythrocyte ghosts/water for benzocaine (BZC), an ester-type always uncharged local anesthetic. The interaction of BZC with EPC liposomes was followed using Electron Paramagnetic Resonance, with spin labels at different positions in the acyl chain (5, 7, 12, 16-doxylstearic acid methyl ester). Changes in lipid organization upon BZC addition allowed the determination of P values, without phase separation. The effect of BZC in decreasing membrane organization (maximum of 11.6% at approx. 0.8:1 BZC:EPC) was compared to those caused by the local anesthetics tetracaine and lidocaine. Hemolytic tests revealed a biphasic (protective/inductive) concentration-dependent hemolytic effect for BZC upon rat erythrocytes, with an effective BZC:lipid molar ratio in the membrane for protection (RePROT), onset of hemolysis (ReSAT) and 100% membrane solubilization (ReSOL) of 1.0:1, 1.1:1 and 1.3:1, respectively. The results presented here reinforce the importance of considering hydrophobic interactions in the interpretation of the effects of anesthetics on membranes.
Pinto
L M
LM
Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, Sao Paulo, Brazil.
Yokaichiya
D K
DK
Fraceto
L F
LF
de Paula
E
E
D020003:1-Octanol / Q000737:chemistry; D000779:Anesthetics, Local / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001566:Benzocaine / Q000737:chemistry* / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004578:Electron Spin Resonance Spectroscopy; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry; D008567:Membranes, Artificial; D008956:Models, Chemical; D010713:Phosphatidylcholines / Q000737:chemistry; D051381:Rats
D000779:Anesthetics, Local; D008081:Liposomes; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; D020003:1-Octanol; D001566:Benzocaine