Differential nerve blockade: esters v. amides and the influence of pKa.

The in vitro sensitivities to local anaesthetic blockade of A, B and C fibres in rabbit vagus nerves were examined using a series of structurally similar amide agents, which varied in lipid solubility and anaesthetic potency. The actions of these drugs were compared with one another, and with those of a series of amino-ester local anaesthetics studied previously. The results demonstrated that A fibres are the most, and C fibres the least, sensitive to blockade by local anaesthetic agents.

Spinal anesthesia in sheep with local anesthetic solutions at pH 4 and pH 7.

Spinal anesthesia was performed in sheep, using five widely-used local anesthetic agents. The durations of sensory and motor block were shortest with procaine and longest with bupivacaine and tetracaine. The durations of block with prilocaine and mepivacaine fell between those of procaine and bupivacaine.

Local anesthetics: 2-N,N-dialkylaminoacyl-2'-methyl (or 2',6'-dimethyl)-4'-butylaminoanilides.

A series of tetracaine analogs based on the lidocaine structure, having a 2'-methyl-(or 2',6'-dimethyl)-4-butylaminoanilide moiety with alpha substitution on the dialkylaminoacyl function, has been synthesized. Local anesthetic activity was found with the N-butyl derivatives in both the 2'-methyl and 2',6'-dimethyl series using both the method of rabbit cornea loss of reflex and spinal anesthesia in sheep. Duration of activity of the compounds was greater than that of lidocaine, but less than that of tetracaine, with comparable dosage levels.

New antiarrhythmic agents. 7. 2,3-Diaminopropionanilides.

A series of 2,3-diaminopropionanilides was synthesized by acylation of mono- and disubstituted aniline derivatives with 2,3-dibromopropionyl chloride and subsequent amination with the appropriate secondary amines. The target compounds were evaluated in mice for antiarrhythmic efficacy against chloroform-induced tachycardia and for central nervous system toxicity. Several of the active agents were found to have much higher antiarrhythmic potencies than lidocaine, but they were also toxic.