Octenidine dihydrochloride

Octenidine dihydrochloride is a cationic surfactant, with a gemini-surfactant structure, derived from 4-aminopyridine. It is active against Gram-positive and Gram-negative bacteria. Since 1987, it has been used primarily in Europe as an antiseptic prior to medical procedures, including on neonates.

Octenidine dihydrochloride^[1]

Names
IUPAC name 1,1′-(Decane-1,10-diyl)bis(N-octylpyridin-4(1H)-imine)—hydrogen chloride (1/2)
Other names N,N′-(decane-1,10-diyldi-1(4H)-pyridyl-4-ylidene)bis(octylammonium) dichloride
Identifiers
CAS Number	70775-75-6 Y Octenidine: 71251-02-0 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:478961
ChEMBL	ChEMBL36342
ChemSpider	46370
ECHA InfoCard	100.068.035
EC Number	274-861-8
PubChem CID	198481
UNII	U84956NU4B Y Octenidine: OZE0372S5A Y
CompTox Dashboard (EPA)	DTXSID90221025
InChI InChI=1S/C36H62N4.2ClH/c1-3-5-7-9-15-19-27-37-35-23-31-39(32-24-35)29-21-17-13-11-12-14-18-22-30-40-33-25-36(26-34-40)38-28-20-16-10-8-6-4-2;;/h23-26,31-34H,3-22,27-30H2,1-2H3;2*1H Key: SMGTYJPMKXNQFY-UHFFFAOYSA-N InChI=1/C36H62N4.2ClH/c1-3-5-7-9-15-19-27-37-35-23-31-39(32-24-35)29-21-17-13-11-12-14-18-22-30-40-33-25-36(26-34-40)38-28-20-16-10-8-6-4-2;;/h23-26,31-34H,3-22,27-30H2,1-2H3;2*1H
SMILES CCCCCCCCN=C1C=CN(C=C1)CCCCCCCCCCN2C=CC(=NCCCCCCCC)C=C2.Cl.Cl
Properties
Chemical formula	C36H64Cl2N4
Molar mass	623.84 g·mol−1
Pharmacology
ATC code	R02AA21 (WHO) A01AB24 (WHO), QA01AB24 (WHO), combination codes: D08AJ57 (WHO), G01AX66 (WHO)
Legal status	EU: Rx-only[2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Medical uses

Since 1987, octenidine has been used in Europe as an antiseptic, in concentrations of 0.1 to 2.0%.^{[citation needed]} It is a substitute for chlorhexidine, with respect to its slow action and concerns about the carcinogenic impurity 4-chloroaniline.^{[citation needed]} Octenidine preparations are less expensive than chlorhexidine and no resistance had been observed as of 2007.^[3] They may contain the antiseptic phenoxyethanol.^[4] It is not listed in the Annex V of authorized preservatives of the European Cosmetic Regulation 1223/2009.

Efficacy

Octenidine dihydrochloride is active against Gram-positive and Gram-negative bacteria.^[5]

In vitro suspension tests with 5 minute exposure time have shown that octenidine requires lower effective concentrations than chlorhexidine to kill common bacteria like Staphylococcus aureus, Escherichia coli, Proteus mirabilis and the yeast Candida albicans.^[6]

Comparison between octenidine and chlorhexidine determined by the suspension test after 5 minutes of exposure.

	Effective concentration, %
	Octenidine dihydrochloride	Chlorhexidine digluconate
Staphylococcus aureus	0.025	>0.2
Escherichia coli	0.025	0.1
Proteus mirabilis	0.025	>0.2
Candida albicans	0.01	0.025
Pseudomonas aeruginosa	0.025	>0.2

An observational study of using octenidine on the skin of patients in 17 intensive care units in Berlin in 2014 showed decreasing nosocomial infection rates.^[7]

In a survey of German neonatal intensive-care units octenidine without phenoxyethanol and octenidine were the most common skin antiseptics used for intensive-care procedures. Skin complications included blistering, necrosis and scarring, which has not been previously reported in this population.^[4]

In a 2016 study of pediatric cancer patients with long-term central venous access devices using octenidine/isopropanol for the disinfection of catheter hubs and 3-way stopcocks as part of a bundled intervention, the risk of bloodstream infections decreased.^[8]

Safety

Octenidine is absorbed neither through the skin, nor through mucous membranes, nor via wounds and does not pass the placental barrier. However, cation-active compounds cause local irritation and are extremely poisonous when administered parenterally.^[6]

In a 2016 in vitro study of mouth rinses on gingival fibroblasts and epithelial cells octenidine showed a less cytotoxic effect, especially on epithelial cells, compared to chlorhexidine after 15 min.^[9] Wound irrigation with octenidine has caused severe complications in dogs,^[10] aseptic necrosis and chronic inflammation in penetrating hand wounds in humans.^[11][12]

Synthesis

The secondary amine (3) is formed by reaction of octan-1-amine (1) and 4-bromopyridine (2). Treatment of this with 1,10-dichlorodecane (4) yields octenidine as its dihydrochloride salt.^[13][14][15]