Anesthetics Close-Up

      While the general anesthetics used to induce complete unconsciousness exist as gases at room temperature, many local anesthetics, which reduce pain by preventing the propagation of nerve signals, are solids. Solutions of varying concentrations of these agents are used clinically, but in their pure state they are crystalline powders. We thought it might be of interest to attempt to photograph crystals of these common local anesthetics using polarized light microscopy, a standard technique in the study of mineral and crystalline specimens.

First, a thin crystalline layer of the anesthetic was grown on a glass microscope slide. This is done by dissolving a small amount of it in an appropriate solvent, in this case water, isopropanol or acetone. As the liquid evaporates the anesthetic recrystallizes to form a translucent layer on the slide, looking somewhat like frost on a windowpane. This process may be completed in just a few seconds, as when benzocaine recrystallizes from an acetone solution, or extend over many days depending upon the substance, solvent and conditions. Alternatively, the anesthetic can be melted; recrystallization occurs as it cools to room temperature.

Polarized light – light whose vibrations have been limited to only one plane – is needed to reveal the color latent within the microcrystals. It's easily produced through the use of two gray plastic polarizing filters. One is placed in the light beam before it passes up through the crystals, and the other is placed on the eyepiece, above the crystals. This latter one is then rotated until the polarizers are "crossed" and a black background is produced. The optically active crystals now shine brightly as they're brought into focus. Their highly-ordered molecular composition and many structural variations interact with the polarized light, selectively altering its wavelengths bringing forth the various colors. By moving the slide the microscopist can now look for interesting and colorful designs to photograph.

We hope you enjoy the results (just click on the names below). Our thanks to Peter Gerner, MD, Ginkgo Wang, PhD and Larry Cogswell for generously providing samples of the anesthetics.

Jamie Bell
Lawrence Tsen, MD
Benzocaine – An ethyl ester of para-aminobenzoic acid, Benzocaine has only limited ability to exist in a form that can block nerve conduction. Nonetheless, it is frequently used as a topical anesthetic in products like throat lozenges.
Lidocaine – Departing from the ester base employed by others, Lofgren ushered in an entirely new class of compounds, the amide local anesthetics, with the discovery of Lidocaine in 1943. Today, it remains among the most popular anesthetics worldwide, and its success has been heralded by the fact that most new anesthetics are amide derivatives.
Procaine (Novocaine) – Quickly following Willstatter's discovery that cocaine, the first local anesthetic known to modern medicine, was an ester compound, Einhorn created Procaine, the first synthetic ester local anesthetic in 1905. Nowadays, as we all know, it's widely used to numb the pain of dental procedures.
Bupivacaine – By adding a three carbon group onto the tertiary amine of Mepivacaine, Bupivacaine was formed; the additional carbon chain made the agent more lipid soluble, more potent, and longer lasting. Currently, it is the predominant local anesthetic used worldwide for obstetric analgesia and anesthesia.
Dibucaine – Belonging to a class of amide local anesthetics known as aminoalkyl amides, Dibucaine has undergone limited investigation as a local anesthetic due to its molecular complexity and significant potency. It has, however, served anesthesiologists well as one of the best tests for atypical forms of plasma "pseudo"-cholinesterase.

We'll be trying a few more as time allows so you may want to check back.

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