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J Biomed Biotechnol ; 2012: 170958, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22778542

RESUMO

Aminoamide local anesthetics induce vasoconstriction in vivo and in vitro. The goals of this in vitro study were to investigate the potency of local anesthetic-induced vasoconstriction and to identify the physicochemical property (octanol/buffer partition coefficient, pKa, molecular weight, or potency) of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction. Cumulative concentration-response curves to local anesthetics (levobupivacaine, ropivacaine, lidocaine, and mepivacaine) were obtained from isolated rat aorta. Regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% (ED(50)) of the local anesthetic-induced maximum vasoconstriction. We determined the order of potency (ED(50)) of vasoconstriction among local anesthetics to be levobupivacaine > ropivacaine > lidocaine > mepivacaine. The relative importance of the independent variables that affect the vasoconstriction potency is octanol/buffer partition coefficient > potency > pKa > molecular weight. The ED(50) in endothelium-denuded aorta negatively correlated with the octanol/buffer partition coefficient of local anesthetics (r(2) = 0.9563; P < 0.001). The potency of the vasoconstriction in the endothelium-denuded aorta induced by local anesthetics is determined primarily by lipid solubility and, in part, by other physicochemical properties including potency and pKa.


Assuntos
Amidas/farmacologia , Anestésicos Locais/farmacologia , Vasoconstritores/farmacologia , Amidas/química , Anestésicos Locais/química , Animais , Aorta/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Peso Molecular , Octanóis/química , Ratos , Ratos Sprague-Dawley , Análise de Regressão , Solubilidade , Vasoconstrição/efeitos dos fármacos , Vasoconstritores/química
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