RAC 421-II, also referred to simply as RAC 421, is a

quaternary The Quaternary ( ) is the current and most recent of the three periods of the Cenozoic Era in the geologic time scale of the International Commission on Stratigraphy (ICS), as well as the current and most recent of the twelve periods of the ...

local anesthetic A local anesthetic (LA) is a medication that causes absence of all sensation (including pain) in a specific body part without loss of consciousness, providing local anesthesia, as opposed to a general anesthetic, which eliminates all sensati ...

that acts through intracellular blockage of the NaKATPase channel.

Function

As a

ammonium Ammonium is a modified form of ammonia that has an extra hydrogen atom. It is a positively charged (cationic) polyatomic ion, molecular ion with the chemical formula or . It is formed by the protonation, addition of a proton (a hydrogen nucleu ...

analogue of another local anesthetic, RAC 109, RAC 421-II is permanently charged and so cannot cross the

hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

. As it cannot

diffuse Diffusion is the net movement of anything (for example, atoms, ions, molecules, energy) generally from a region of higher concentration to a region of lower concentration. Diffusion is driven by a gradient in Gibbs free energy or chemical p ...

across the cell membrane, it cannot exert its inhibitory effects on the intracellular surface of NaKATPase. As such, it can only exert its anesthetic properties if it is injected into the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

of the

nerve fibre An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see spelling differences) is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action pote ...

. Inhibition occurs through allowing the

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

and

potassium Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...

gradients across the cell membrane to dissipate. NaKATPase blockage preferentially inhibits firing of

nociceptive In physiology, nociception , also nocioception; ) is the sensory nervous system's process of encoding noxious stimuli. It deals with a series of events and processes required for an organism to receive a painful stimulus, convert it to a molecular ...

nerve fibres due to their relatively low cell diameter and so low tolerance to NaKATPase inhibitors. This is in contrast to non-quaternary anesthetics like

benzocaine Benzocaine, sold under the brand name Orajel amongst others, is a local anesthetic, belonging to the amino ester drug class, commonly used as a topical painkiller or in cough drops. It is the active ingredient in many over-the-counter ...

and

tetracaine Tetracaine, also known as amethocaine, is an ester local anesthetic used to numb the eyes, nose, or throat. It may also be applied to the skin before starting intravenous therapy to decrease pain from the procedure. Typically it is applied as a l ...

which cross the cell membrane in their uncharged states and so they can induce anesthetic effects upon application to the extracellular side of the membrane. They subsequently become charged and so activated within the cytosol to exert their inhibitory effects on NaKATPase (NaKATPase inhibiting anesthetics must be in their charged state to become active).

References

{{reflist Local anesthetics Pyrrolidones Spiro compounds Tetralins