Selective relaxant binding agents (SRBAs) are a new class of

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

s that selectively encapsulates and binds

neuromuscular blocking agent Neuromuscular-blocking drugs, or Neuromuscular blocking agents (NMBAs), block transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished via their action on the post-synaptic acetylcho ...

s (NMBAs). The first drug introduction of an SRBA is

sugammadex Sugammadex, sold under the brand name Bridion, is a medication for the reversal of neuromuscular blockade induced by rocuronium and vecuronium in general anaesthesia. It is the first selective relaxant binding agent (SRBA). It is marketed by ...

. SRBAs exert a

chelating Chelation () is a type of bonding of ions and their molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These l ...

action that effectively terminates an NMBA ability to bind to

nicotinic receptor Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...

s. Examples of SRBAs include: 1. Sugammadex is a modified gamma cyclodextrin that specifically encapsulates and binds the aminosteroid NMBAs: affinity is highest for

rocuronium Rocuronium bromide (brand names Zemuron, Esmeron) is an aminosteroid non-depolarizing neuromuscular blocker or muscle relaxant used in modern anaesthesia to facilitate tracheal intubation by providing skeletal muscle relaxation for surgery o ...

, followed by

vecuronium Vecuronium bromide, sold under the brand name Norcuron among others, is a medication used as part of general anesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation. It is also used to help with endotracheal ...

, and relatively low affinity for

pancuronium Pancuronium (trademarked as Pavulon) is an aminosteroid muscle relaxant with various medical uses. It is used in euthanasia and is used in some states as the second of three drugs administered during lethal injections in the United States. Mech ...

. 2. Adamgammadex is also a modified gamma-cyclodextrin, with acetyl-amino groups replacing the carboxylic acid groups of sugammadex. Early research suggests it may have a lower incidence of adverse reactions than sugammadex 3. Calabadion 1 and calabadion 2 are cucurbituril molecules with high binding affinity for both aminosteroid and benzylisoquinoline muscle relaxants. Calabadion 2 has 89 times the affinity for rocuronium than does sugammadex.

Discovery of SRBAs

The discovery of SRBA as a new class of drug is the result of work done by Organon laboratories at the Newhouse research site in

Scotland Scotland is a Countries of the United Kingdom, country that is part of the United Kingdom. It contains nearly one-third of the United Kingdom's land area, consisting of the northern part of the island of Great Britain and more than 790 adjac ...

Cyclodextrin Cyclodextrins are a family of cyclic oligosaccharides, consisting of a macrocycle, macrocyclic ring of glucose subunits joined by α-1,4 glycosidic bonds. Cyclodextrins are produced from starch by enzyme, enzymatic conversion. They are used in ...

s were explored as a means to solubilize rocuronium bromide (a

steroidal A steroid is an organic compound with four fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membr ...

NMBA) in a neutral aqueous solution. Upon creating numerous modified cyclodextrins, one particular

molecule A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

was found to possess extremely high affinity for the rocuronium molecule. Originally known as Org25969, it is now generically named sugammadex sodium.

References

{{Acetylcholine receptor modulators Anesthesia Antidotes Polysaccharides