Studies on Mechanical Actions of Mepivacaine (Carbocaine®) and its Optically Active Isomers on Isolated Smooth Muscle: Role of Ca++and Cyclic AMP

Abstract:The effects of the local anaesthetic mepivacaine and its optically active isomers on mechanical activity, as well as the uptake and mobilization of Ca++, on phosphorylase and phosphodiesterase activity and on the content of cyclic AMP have been studied in smooth muscle. In low concentrations L(+)‐mepivacaine had a contracting action on the rat portal vein and the guinea pig taenia coli, whereas D(‐)‐mepivacaine had a predominantly relaxing action. The contracting action was probably associated with a mobilization of tissue bound Ca++. In higher concentrations both isomers had a marked relaxing action, the D(‐)‐isomer being the most potent. The relaxation was competitively counteracted by Ca++, Ba++and Sr++, but not by K+, histamine or noradrenaline. The uptake of45Ca++was reduced; D(‐)‐mepivacaine tended to be more potent than L(+)‐mepivacaine. The content of cyclic AMP was increased by DL‐mepivacaine in taenia coli and by L(+)‐mepivacaine, but not by D(‐)‐mepivacaine in the portal vein. During isometric conditions of taenia coli the increased content of cyclic AMP was partly caused by an adrenergic β‐receptor stimulation and partly by a Ca++‐depending reduction of the phosphodiesterase activity.