Synthesis and local anesthetic properties of secondary alkoxyalkylaminoacylanilides.

Nineteen secondary alkoxyalkylaminoacylanilides were prepared. They were weaker bases and were more hydrophilic than the corresponding analogs lacking the ether function. In 2% solution, these compounds blocked the rat sciatic nerve in vivo after relatively short onset times with good frequency of anesthesia. The duration of block was 0.4--1.5 times that of lidocaine. Their systemic toxicity was low, and their irritation liability in most instances was acceptable.

The clinical character of local anesthetics: a function of frequency-dependent conduction block.

It is clinically recognized fact that some local anesthetics have a proclivity for inhibition of motor nerves, while others preferentially affect sensory and sympathetic fibers. On the basis that sensory fibers have a frequency threshold for transmission of nociceptive stimuli and that somatic motor fibers have no such frequency threshold, we hypothesized that this variation may be due to differences in the effect of local anesthetics on axonal refractory period. Frog sciatic nerves were partially blocked with lidocaine, bupivacaine, tetracaine and etidocaine, and then stimulated in trains of 17 pulses, at frequencies between 3 and 100 Hz. The height and area of the last action potential in a train were measured. At a comparable level of partial block (50% at 100 Hz), tetracaine and etidocaine showed only a 10% difference between 3 and 100 Hz, while with bupivacaine and lidocaine there was a 30% drop between these two frequencies. This excellent correlation between the laboratory and clinical phenomenon supports our hypothesis. Local anesthetics which have a minimal effect on the refractory period yield enhanced motor block; whereas local anesthetics with a large effect on the refractory period are relatively more potent blockers of sensory and sympathetic transmission.

Separation and partial characterization of surface-active fractions from mouse and rat lung homogenates. Identification of a possible marker system for pulmonary surfactant.

The purpose of this study was to identify a "marker system" for pulmonary surfactant. A density gradient centrifugation procedure was developed to concentrate the surface-active material in mouse and rat lung homogenates. These fractions contained morphologic variants of surfactant such as lamellar bodies and tubular myelin. Lipid and protein analyses were consistent with other techniques indicating that these preparations were surface active. A comparison of the nonspecific esterases in these and other surfact-active preparations (i.e., pulmonary lavage fluid and isolated type II cells) allowed the identification of certain surfactant-associated esterases which are distinguishable electrophoretically and cytochemically from the other pulmonary esterases and which, therefore, may be used as "markers" for surfactant. Possible uses for these enzyme markers in studies of (a) the sites of synthesis and routes of clearance of surfactant and (b) the assessment of variations in surface activity due to either diseases such as the respiratory distress syndrome or to experimental manipulation are discussed.

Chemcial anatomy of the nerve membrane.

The molecular mechanisms involved in the generation and conduction of nerve impulses are still matters for conjecture. The molecular models which have been developed to explain the structure of nerve membrane are reviewed. The chemical composition of the axolemma and how this compares with other membranes is discussed. Modern spectroscopic techniques allow the measurement of non-electrical dynamic changes that occur during nerve conduction. These indicate that the chemical components of nerve membrane are in a very fluid state. Detailed knowledge of the kinds of molecules involved is necessary to understand properly both nerve conduction and nerve block.